Handful of nut consumption each day linked to reduced risk for wide range of diseases

A large analysis of current research shows that people who eat at least 20g of nuts a day have a lower risk of heart disease, cancer and other diseases.

The analysis of all current studies on nut consumption and disease risk has revealed that 20g a day - equivalent to a handful - can cut people's risk of coronary heart disease by nearly 30 percent, their risk of cancer by 15 percent, and their risk of premature death by 22 percent.

An average of at least 20g of nut consumption was also associated with a reduced risk of dying from respiratory disease by about a half, and diabetes by nearly 40 percent, although the researchers note that there is less data about these diseases in relation to nut consumption.

The study, led by researchers from Imperial College London and the Norwegian University of Science and Technology, is published in the journal BMC Medicine.

The research team analysed 29 published studies from around the world that involved up to 819,000 participants, including more than 12,000 cases of coronary heart disease, 9,000 cases of stroke, 18,000 cases of cardiovascular disease and cancer, and more than 85,000 deaths.

While there was some variation between the populations that were studied, such as between men and women, people living in different regions, or people with different risk factors, the researchers found that nut consumption was associated with a reduction in disease risk across most of them.

Study co-author Dagfinn Aune from the School of Public Health at Imperial said: "In nutritional studies, so far much of the research has been on the big killers such as heart diseases, stroke and cancer, but now we're starting to see data for other diseases.

"We found a consistent reduction in risk across many different diseases, which is a strong indication that there is a real underlying relationship between nut consumption and different health outcomes. It's quite a substantial effect for such a small amount of food."

The study included all kinds of tree nuts, such as hazel nuts and walnuts, and also peanuts - which are actually legumes. The results were in general similar whether total nut intake, tree nuts or peanuts were analysed.

What makes nuts so potentially beneficial, said Aune, is their nutritional value: "Nuts and peanuts are high in fibre, magnesium, and polyunsaturated fats - nutrients that are beneficial for cutting cardiovascular disease risk and which can reduce cholesterol levels.

"Some nuts, particularly walnuts and pecan nuts are also high in antioxidants, which can fight oxidative stress and possibly reduce cancer risk. Even though nuts are quite high in fat, they are also high in fibre and protein, and there is some evidence that suggests nuts might actually reduce your risk of obesity over time."

The study also found that if people consumed on average more than 20g of nuts per day, there was little evidence of further improvement in health outcomes.

The team are now analysing large published datasets for the effects of other recommended food groups, including fruits and vegetables, on a wider range of diseases.

Ref : http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0730-3

Combination treatment produces better outcomes in erythropoietin-refractory MDS patients, study shows

In continuation of my updates  lenalidomide

Patients with myelodysplastic syndromes (MDS) suffer from a reduction in the number of different types of blood cells, including red blood cells leading to the development of anemia. Many patients with lower-risk MDS benefit from treatment with recombinant-erythropoietin (rHuEPO), which stimulates blood cell production. However, patients who become refractory to rHuEPO have few effective treatment options.

 

Alan F. List, M.D., president and CEO of Moffitt Cancer Center, will present interim results from the phase 3 ECOG-ACRIN E2905 Intergroup Study at the American Society of Hematology Annual Meeting in San Diego. The study shows that lenalidomide in combination with epoetin alpha produced better outcomes and similar toxicity as lenalidomide alone in patients with erythropoietin-refractory, lower-risk myelodysplastic syndromes (MDS).

Early phase clinical trials have demonstrated that lenalidomide improves blood cell production in transfusion-dependent non-del(5q) MDS, leading to transfusion-dependence in 26 percent of patients. Additionally, data from a pilot trial suggested that lenalidomide in combination with epoetin alpha may overcome resistance and improve response rates in erythropoietin-refractory MDS patients.

This observation led to the initiation of a phase 3 trial to assess if lenalidomide combined with epoetin alpha improves the major erythroid response rate after 4 cycles of treatment when compared to lenalidomide alone in patients with low or intermediate-1 risk MDS who were unresponsive to rHuEPO treatment or were transfusion-dependent with serum erythropoietin levels greater than 500 mU/mL.

An interim analysis of 163 patients randomized to lenalidomide (n = 81) or lenalidomide + epoetin alpha (n = 82) showed that the study met the predefined stopping criteria. Lenalidomide + epoetin alpha treatment resulted in significantly better erythroid responses than lenalidomide alone among 116 evaluable patients, with a major erythroid response rate at 16 weeks of 33.3 percent for lenalidomide + epoetin alpha and 14.3 percent for lenalidomide alone. The treatment groups had similar rates and types of grade 3 or higher non-hematologic adverse events. Additionally, a biomarker analysis of responding patients suggested that the erythroid CD45 isoform may predict response to combination treatment.

More  at Medical News

CBD oil may reduce frequency and severity of seizures in patients with epilepsy, UAB study shows

Cannabidiol oil, also known as CBD oil, reduces the frequency and severity of seizures in children and adults with severe, intractable epilepsy, according to findings presented by researchers from the University of Alabama at Birmingham at the American Epilepsy Society 70th Annual Meeting.

UAB researchers presented eleven abstracts, or research findings, at the meeting. A key finding was that CBD provided a significant reduction in frequency of seizures for a majority of the patients in the study, and that approximately two-thirds of patients saw a greater than 50 percent reduction in severity.

"It is encouraging that both frequency and severity of seizures appear to improve in the majority of patients in our study, patients who have limited treatment options," said Jerzy P. Szaflarski, M.D., Ph.D., professor in the Department of Neurology and director of the UAB Epilepsy Center. "Our research adds to the evidence that CBD may reduce frequency of seizures, but we also found that it appears to decrease the severity of seizures, which is a new finding."

The results were based on an open-label study of 81 patients — 42 children and 39 adults — who experienced four or more seizures per month. UAB launched the studies of CBD oil as a treatment for severe, intractable seizures in April 2015. The studies, an adult study at UAB and a pediatric study at Children's of Alabama, were authorized by the Alabama Legislature in 2014 by legislation known as Carly's Law.

After one month of beginning CBD therapy, 68 percent of the patients had experienced a greater than 25 percent reduction in seizure frequency; 58 percent had a greater than 50 percent reduction; 36 percent had a greater than 75 percent reduction and 9 percent were seizure-free. Those results were maintained at three and six months.

To assess seizure severity, researchers led by Jenifer DeWolfe, M.D., associate professor of neurology, used the Chalfont Seizure Severity Scale, a questionnaire given prior to therapy and re-administered at intervals throughout treatment. Fifty-seven patients were followed for three months: 67 percent experienced a more than 50 percent decrease in seizure severity, while 33 percent did not. Of 47 patients followed for six months, 64 percent had a greater than 50 percent decrease in seizure severity and 36 percent did not.

"These are encouraging results, but it is important to note that each patient may respond differently to CBD, and the dose for optimal seizures control varies," said Martina Bebin, M.D., professor of neurology and co-primary investigator of the CBD studies. "There appears to be an optimal CBD dose range where the patient achieves maximum benefit. If outside this CBD dosing range, the seizure frequency may not improve and may even increase. More research is needed, including determining why and how CBD helps some people with epilepsy but not others."

Among the other UAB abstracts presented at the AES meetings:

•CBD oil was associated with an improvement in mood, an effect independent of the extent of seizure reduction. Lead author Pongkiat Kankirawatana, M.D., professor of pediatrics, says CBD oil may have overall positive effects on mood, which should be further investigated in patients with epilepsy and other chronic conditions in controlled studies.

•A study led by Szaflarski and Bebin found that the optimum dose in both children and adults was between 20 and 25 mg/kg/day.

•Jane Allendorfer, M.D., assistant professor of neurology, found that CBD, in a selected group of patients with epilepsy who experienced overall improved seizure control, has the potential for positive cognitive effects that are associated with corresponding fMRI signal changes.

•One abstract reports on an interaction between warfarin, a drug used as an anticoagulant, and CBD. This underscores the importance of monitoring appropriate laboratory work in patients receiving CBD oil along with other medications, according to study lead Brannon Vines, M.D., a clinical neurophysiology fellow.

•Significant drug interactions were identified between CBD and commonly-used medications for epilepsy, including clobazam, rufinamide, topiramiate, zonisamide and eslicarbazepine. This study, led by neurology fellow Tyler Gaston, M.D., emphasizes the importance of monitoring anti-epilepsy drug levels during treatment with CBD.

•Electrical discharges measured by EEG decreased significantly after initiation and maintenance of CBD, particularly in pediatric patients, according to a study led by Leslie Grayson, M.D., a neurology fellow.

•Using fMRI imaging, Amber Gregory, a graduate student in psychology, showed that persons with epilepsy showed gains in working memory that were associated with a shift in neural recruitment as examined with functional MRI.

•An abstract aimed at examining associations between social determinants of health, such as age, gender and socioeconomic factors against health status, quality of life and mood states showed that higher age and low income were associated with lower health ratings among epilepsy patients, according to study led Magdalena Szaflarski, Ph.D., assistant professor of sociology.

The studies are designed to test the safety and tolerability of CBD oil in patients with intractable seizures. CBD oil, a derivative of the cannabis plant, is delivered orally as an oily liquid.

The oil used in the studies is produced under stringent requirements of the United States Food and Drug Administration by a licensed pharmaceutical company. It contains only traces of THC, the psychoactive component of marijuana. The process developed by GW Pharmaceuticals guarantees the consistency of the product that is provided to study participants. 

For details read at the link

New anti-inflammatory drug reduces death of existing brain cells then repairs damage after stroke

Researchers at The University of Manchester have discovered that a potential new drug reduces the number of brain cells destroyed by stroke and then helps to repair the damage.

A reduction in blood flow to the brain caused by stroke is a major cause of death and disability, and there are few effective treatments.

A team of scientists at The University of Manchester has now found that a potential new stroke drug not only works in rodents by limiting the death of existing brain cells but also by promoting the birth of new neurones (so-called neurogenesis).  

This finding provides further support for the development of this anti-inflammatory drug, interleukin-1 receptor antagonist (IL-1Ra in short), as a new treatment for stroke. The drug is already licensed for use in humans for some conditions, including rheumatoid arthritis. Several early stage clinical trials in stroke with IL-1Ra have already been completed in Manchester, though it is not yet licensed for this condition.

In the research, published in the biomedical journal Brain, Behavior and Immunity, the researchers show that in rodents with a stroke there is not only reduced brain damage early on after the stroke, but several days later increased numbers of new neurones, when treated with the anti-inflammatory drug IL-1Ra.

Previous attempts to find a drug to prevent brain damage after stroke have proved unsuccessful and this new research offers the possibility of a new treatment.

Importantly, the use of IL-1Ra might be better than other failed drugs in stroke as it not only limits the initial damage to brain cells, but also helps the brain repair itself long-term through the generation of new brain cells.

These new cells are thought to help restore function to areas of the brain damaged by the stroke. Earlier work by the same group showed that treatment with IL-1Ra does indeed help rodents regain motor skills that were initially lost after a stroke. Early stage clinical trials in stroke patients also suggest that IL-1Ra could be beneficial.

The current research is led by Professor Stuart Allan, who commented: "The results lend further strong support to the use of IL-1Ra in the treatment of stroke, however further large trials are necessary."

Walnuts could be key to happier state-of-mind in young healthy men

In continuation of my update on walnuts

College can be a stressful time for young adults as they figure out how to manage intense daily routines that include work, study and play. Eat well, exercise and get plenty of sleep is a familiar mantra to alleviate this stress, but now with the results of his latest study, UNM Nutrition Professor Peter Pribis is able to tell college students that walnuts could be a key to a happier state-of-mind. 

In this first intervention study in humans, Pribis measured the effect of walnut consumption on mood.

"In the past, studies on walnuts have shown beneficial effects on many health outcomes like heart disease, diabetes and obesity," said Pribis. "Our study was different because we focused on cognition, and in this controlled randomized trial (CRT) we measured mood outcomes in males and females."

The participants of the study were 64 students between the ages of 18-25. They represented most ethnic groups: Caucasian, African American, Hispanic and Asian.

The participants were asked to eat three slices of banana bread every day for sixteen weeks--eight weeks of banana bread with walnuts and eight weeks of banana bread without walnuts. The nuts were finely ground into the dough so the two banana breads were similar in taste and appearance. While eating banana bread with walnuts the participants consumed half a cup of walnuts daily.

The mood of the students was measured at the end of each eight-week period.

"We used a validated questionnaire called Profiles of Mood States (POMS)," says Pribis. "It is one of the most widely used and accepted mood scales in studies on cognition. The test has six mood domains: tension, depression, anger, fatigue, vigor, confusion and also provides a Total Mood Disturbance score (TMD). The lower the TMD score the better the mood."

In this double-blind, randomized, placebo controlled, cross-over feeding trial with walnuts for eight weeks, Pribis observed a significant improvement in mood in young, healthy males.

"There was a meaningful, 28 percent improvement of mood in young men," said Pribis. "However we did not observe any improvement of mood in females. Why this is we do not know."

There are several nutrients in walnuts that could be responsible for the improved mood like alpha-Linolenic acid, vitamin E, folate, polyphenols or melatonin. However, this was a whole food study, so in the end it was the synergy and interaction of all the nutrients in the walnuts combined.

For Pribis, the lesson learned from this food study is clear, "Eat more walnuts. This is an easy intervention. They're not only good for your mood, but overall health as well. The recommended amount is one handful per day."

With this knowledge in hand--and hopefully walnuts in the other--young men can happily tackle life's daily stress.

Ref: http://news.unm.edu/news/the-key-to-a-better-mood-for-young-men-is-a-nut




Read more at ..

New drug receives FDA approval to reduce risk of cardiovascular death in adults with diabetes

The U.S. Food and Drug Administration today approved a new indication for Jardiance (empagliflozin) to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and cardiovascular disease.

"Cardiovascular disease is a leading cause of death in adults with type 2 diabetes mellitus," said Jean-Marc Guettier, M.D., C.M., director of the Division of Metabolism and Endocrinology Products in FDA's Center for Drug Evaluation and Research. "Availability of antidiabetes therapies that can help people live longer by reducing the risk of cardiovascular death is an important advance for adults with type 2 diabetes."

According to the Centers for Disease Control and Prevention, death from cardiovascular disease is 70 percent higher in adults with diabetes compared to those without diabetes, and patients with diabetes have a decreased life expectancy driven in large part by premature cardiovascular death.

The FDA's decision is based on a postmarketing study required by the agency when it approved Jardiance in 2014 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Jardiance was studied in a postmarket clinical trial of more than 7,000 patients with type 2 diabetes and cardiovascular disease. In the trial, Jardiance was shown to reduce the risk of cardiovascular death compared to a placebo when added to standard of care therapies for diabetes and atherosclerotic cardiovascular disease.

Jardiance can cause dehydration and low blood pressure (hypotension). Jardiance can also cause increased ketones in the blood (ketoacidosis), serious urinary tract infection, acute kidney injury and impairment in renal function, low blood glucose (hypoglycemia) when used with insulin or insulin secretagogues (e.g. sulfonylurea, a medication used to treat type 2 diabetes by increasing the release of insulin in the pancreas), vaginal yeast infections and yeast infections of the penis (genital mycotic infections), and increased cholesterol.

The most common side effects of Jardiance are urinary tract infections and female genital infections.

Jardiance is not intended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Jardiance is contraindicated in patients with a history of serious hypersensitivity reactions to Jardiance, severe renal impairment, end-stage renal disease, or dialysis.

Arthritis drug increases effectiveness of antidepressants in bipolar patients

In continuation of my updates on celecoxib

Giving severely depressed patients the arthritis drug celecoxib (Celebrex®) dramatically boosted the effectiveness of their antidepressant medication, a Loyola study has found. 

Loyola Medicine psychiatrist Angelos Halaris, MD, PhD, presented the study at the Fifth International Congress on Psychiatry and the Neurosciences in Athens, Greece. Dr. Halaris is a professor in the Department of Psychiatry and Behavioral Neurosciences of Loyola University Chicago Stritch School of Medicine. 

 The eight-week study enrolled bipolar adults, aged 18 to 65, who were in the depressive phase of their disease and had not benefitted from an antidepressant. (Bipolar disorder is marked by alternating periods of elation and depression, with depression typically lasting longer.) Patients were randomly assigned to receive the antidepressant escitalopram (Lexapro®) plus celecoxib or Lexapro plus a placebo. 

Seventy-eight percent of the patients in the celecoxib group experienced at least a 50 percent reduction in their depression scores, with 63 percent reporting their depression had gone away completely. By comparison, only 45 percent of the placebo group recorded a 50 percent or more reduction in depression, with only 10 percent reporting their depression had lifted completely.

It typically takes four to six weeks before an antidepressant begins working. In the Loyola study, patients who took celecoxib began seeing a benefit from their antidepressant within a week.
Fifty-five patients completed the study: 31 in the Lexapro plus celecoxib group and 24 in the Lexapro plus placebo group. 

Previous studies have found that depression revs up the immune system, resulting in chronic inflammation. This inflammatory response affects the normal balance of chemical messengers in the brain called neurotransmitters. Inflammation hinders the function of antidepressants that are designed to restore normal chemical balance. By fighting inflammation, celecoxib appears to make antidepressants more effective, Dr. Halaris said. 

 Celecoxib is used to treat pain, redness, swelling and inflammation from arthritis. It also can manage acute pain and menstrual cramps. By itself, it does not treat depression.

 The study's findings support the hypothesis that inflammation plays a critical role in depression. Reducing inflammation with a drug such as celecoxib "reverses treatment resistance and enhances overall antidepressant response," Dr. Halaris wrote in the study. "Such an intervention, if implemented relatively early in the course of the disease, may arrest the neuroprogressive course of bipolar disorder." 

Scientists modify structure of cancer drug to enhance ability to pass through blood-brain barrier

In efforts to develop new treatments for brain cancer, scientists from Johns Hopkins Drug Discovery and the Kimmel Cancer Center's Bloomberg~Kimmel Institute for Cancer Immunotherapy report they have altered the structure of an experimental drug that seems to enhance its ability to slip through the mostly impermeable blood-brain barrier. Results of their proof-of-concept experiments in monkeys, published Aug. 25 in the Journal of Medicinal Chemistry, show a tenfold better delivery of the drug to the brain compared with the rest of animals' bodies.

The scientists began with an experimental anti-cancer drug cultivated from bacteria found in Peruvian soil more than 70 years ago. Called 6 diazo-5-oxo L norleucine, or DON, the drug blocks the cellular use of the protein building block glutamine. On its own, DON has shrunk tumors in clinical trials of people with a variety of advanced cancers, but its damage to the gastrointestinal system, a glutton for glutamine, ultimately proved too toxic for humans, say the scientists.

"We wondered whether we could make a safer and more tolerable form of DON by enhancing its brain penetration and limiting its exposure to the rest of the body and, thus, toxicity," says Barbara Slusher, Ph.D., professor of neurology, medicine, psychiatry, neuroscience and oncology at the Johns Hopkins University School of Medicine and director of Johns Hopkins Drug Discovery.

Slusher teamed up with Johns Hopkins Kimmel Cancer Center immunologist Jonathan Powell, M.D., Ph.D., who has studied how cancer cells use different metabolic pathways to evade destruction by immune cells.

"A tumor uses aggressive metabolism to grow, sucking up all the surrounding nutrients, which leads to a very oxygen-poor, acidic environment that is not conducive to cancer-killing immune cells," says Powell, who is an associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

Powell suspects that using glutamine-blocking drugs to target tumor metabolism could make the environment around a tumor less harsh, slow down its growth and give the immune system a chance to attack the cancer cells. "The hope is to enhance certain immunotherapy drugs by adding such glutamine antagonists," says Powell.

To alter DON, Slusher and her drug discovery team designed and synthesized various derivatives, focused on making the drug more lipid soluble, or lipophillic, a trait known to aid passage through the blood-brain barrier. Once inside the brain, the new derivatives are designed to rapidly metabolize back to DON.

They gave DON and an altered derivative, dubbed 5c, intravenously to two monkeys and, 30 minutes later, measured the amount of the drugs in the monkeys' cerebrospinal fluid and circulating plasma, which is the liquid portion of blood that remains after blood cells, platelets and other cellular components are removed. The monkey that received DON had about seven times less concentration of the drug in its blood than the monkey that received 5c. In the monkey that received 5c, which converts to DON in the brain, the scientists found 10 times more DON in the cerebrospinal fluid than the monkey treated with unaltered DON.

"We showed that we can modify these drugs to have further specificity to target the brain and limit toxicity to the rest of the body," says Slusher. "This strategy can potentially be used to develop tailored drugs for different cancers."

Scientists modify structure of cancer drug to enhance ability to pass through blood-brain barrier:

U.S. FDA panel narrowly backs Cempra's antibiotic solithromycin

A panel of federal health advisers has narrowly recommended approval for an experimental antibiotic from Cempra Inc., a small North Carolina drugmaker.

The Food and Drug Administration's outside experts voted 7-6 in favor of the drug, saying its effectiveness outweighed risks of liver toxicityseen in company studies. The vote is nonbinding but the FDA often follows the advice of its panelists.

Cempra is one of a handful of drugmakers developing new antibiotics amid growing bacterial resistance to decades-old drugs like penicillin.

On Wednesday Cempra shares plunged more than 60 percent after the FDA posted an online review highlighting irregular liver enzyme measurements reported with the drug, called solithromycin. 

U.S. FDA panel narrowly backs Cempra's antibiotic solithromycin

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

A new compound, discovered jointly by international pharmaceutical company Servier, headquartered in France, and Vernalis (R&D), a company based in the UK, has been shown by researchers at the Walter and Eliza Hall Institute and Servier to block a protein that is essential for the sustained growth of up to a quarter of all cancers.

The research presents a new way to efficiently kill these cancerous cells and holds promise for the treatment of blood cancers such as acute myeloid leukemia, lymphoma and multiple myeloma, as well as solid cancers such as melanoma and cancers of the lung and breast. It is published online in the journal Nature.

The Servier compound -- S63845 -- targets a protein of the BCL2 family, called MCL1, which is essential for the sustained survival of these cancer cells.

Institute scientist Associate Professor Guillaume Lessene, who led the Walter and Eliza Hall Institute's research team in Melbourne, Australia, said the work provided the first clear preclinical evidence that inhibiting MCL1 was effective in targeting several cancer types.

"MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body," Associate Professor Lessene said. "Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival."

The institute team of Associate Professor Lessene worked with haematologist Associate Professor Andrew Wei and Dr Donia Moujalled from The Alfred Hospital and Servier scientists, to demonstrate that not only was S63845 effective against several cancer types, but that it could also be delivered at doses that were well tolerated by normal cells.

Dr Olivier Geneste, Director of Oncology Research at Servier, said this preclinical research represented major findings regarding the druggability of MCL1, a valuable and highly challenging target. "S63845 was discovered through collaboration with the fragment and structure based discovery expertise at Vernalis," he said. "As part of the ongoing Servier / Novartis collaboration on this target class, clinical development of a MCL1 inhibitor should be launched in the near future."

Associate Professor Lessene said the research provided further evidence of the usefulness of a new class of anti-cancer drugs called BH3 mimetics. "BH3 mimetics inhibit a group of proteins known as the 'pro-survival BCL-2 proteins'," he said. "MCL1 is a member of this protein family, and inhibiting it activates the process of programmed cell death. Walter and Eliza Hall Institute researchers revealed the role of BCL-2 in cancer more than 28 years ago and the essential role of MCL1 for the survival of malignant cells four years ago."

Ref : 

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models : Nature : Nature Research

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

A new compound, discovered jointly by international pharmaceutical company Servier, headquartered in France, and Vernalis (R&D), a company based in the UK, has been shown by researchers at the Walter and Eliza Hall Institute and Servier to block a protein that is essential for the sustained growth of up to a quarter of all cancers.

The research presents a new way to efficiently kill these cancerous cells and holds promise for the treatment of blood cancers such as acute myeloid leukemia, lymphoma and multiple myeloma, as well as solid cancers such as melanoma and cancers of the lung and breast. It is published online in the journal Nature.

The Servier compound -- S63845 -- targets a protein of the BCL2 family, called MCL1, which is essential for the sustained survival of these cancer cells.

Institute scientist Associate Professor Guillaume Lessene, who led the Walter and Eliza Hall Institute's research team in Melbourne, Australia, said the work provided the first clear preclinical evidence that inhibiting MCL1 was effective in targeting several cancer types.

"MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body," Associate Professor Lessene said. "Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival."

The institute team of Associate Professor Lessene worked with haematologist Associate Professor Andrew Wei and Dr Donia Moujalled from The Alfred Hospital and Servier scientists, to demonstrate that not only was S63845 effective against several cancer types, but that it could also be delivered at doses that were well tolerated by normal cells.

Dr Olivier Geneste, Director of Oncology Research at Servier, said this preclinical research represented major findings regarding the druggability of MCL1, a valuable and highly challenging target. "S63845 was discovered through collaboration with the fragment and structure based discovery expertise at Vernalis," he said. "As part of the ongoing Servier / Novartis collaboration on this target class, clinical development of a MCL1 inhibitor should be launched in the near future."

Associate Professor Lessene said the research provided further evidence of the usefulness of a new class of anti-cancer drugs called BH3 mimetics. "BH3 mimetics inhibit a group of proteins known as the 'pro-survival BCL-2 proteins'," he said. "MCL1 is a member of this protein family, and inhibiting it activates the process of programmed cell death. Walter and Eliza Hall Institute researchers revealed the role of BCL-2 in cancer more than 28 years ago and the essential role of MCL1 for the survival of malignant cells four years ago."

Ref : 

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models : Nature : Nature Research

Combination of two drugs could be effective strategy to target T-cell lymphocytic leukemia

Researchers have determined that two Phase 1 drugs (CX-4945 and JQ1) can work together to efficiently kill T-cell acute lymphoblastic leukemia cells while having minimal impact on normal blood cells.

 JQ1     CX-4945

Although both drugs were previously tested as single agents in clinical trials to treat cancers, the success of the combined actions on cancer cells was previously unknown until now. The findings appear in the journal Haematologica.

Acute lymphoblastic leukemia, also known as acute lymphocytic leukemia or acute lymphoid leukemia, is a form of cancer of the white blood cells, characterized by the overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblasts. Despite treatment improvement, T-cell leukemia remains fatal in 20 percent of pediatric and 50 percent of adult patients. Both CX-4945 and JQ1 are in clinical trials now as single agents to treat solid and hematological cancers.

"Previous studies provided us a rationale to test the combination of CX-4945 and JQ1 on refractory/relapsed T-cell leukemia," said corresponding author Hui Feng, MD, PhD, assistant professor of pharmacology & experimental therapeutics at Boston University School of Medicine (BUSM). "Our findings suggest that the combination treatment of CX-4945 and JQ1 could be an effective strategy to target refractory/relapsed T-cell leukemia," she added.

According to the researchers the efficacy of using a combination of JQ1 and CX-4945 in treating other cancers should also be investigated.

Ref : http://www.haematologica.org/content/early/2016/10/03/haematol.2016.154013

Cranberry extract disrupts communication between bacteria linked to pervasive infections

In continuation of my update on cranberry

Scientists from McGill University and INRS-Institut Armand-Frappier in Canada recently released a novel investigation showing that cranberry extract successfully interrupted the communication between bacteria associated with problematic and pervasive infections. The authors of the data published in Nature's Scientific Reports, Eric Déziel, professor-investigator at INRS-Institut Armand-Frappier and Nathalie Tufenkji, professor at McGill University, state that not only do the results provide insights into how cranberry compounds may work, they also have implications for the development of alternative approaches to control infections.

Previously published work has shown that the American cranberry (Vaccinium macrocarpon L) contains compounds -- such as proanthocyanidins (PACs) -- that provide meaningful antioxidant, anti-adhesion and anti-microbial properties that help fend off illness. Given this, the scientific team hypothesized that cranberries may also have an anti-virulence potential. They wanted to know if these cranberry compounds could help manage bacterial infections. By feeding fruit flies -- a commonly used model for studying human infections -- cranberry extract, the team discovered that cranberry provided flies protection from a bacterial infection and they lived longer than their cranberry-free counterparts. In essence, the cranberry extract reduced the severity of the bacterial infection.

Study author, Dr. Tufenkji, elaborates on what this might mean for humans, as opposed to flies, "This means that cranberries could be part of the arsenal used to manage infections and potentially minimize the dependence on antibiotics for the global public."

To further explain cranberries' impact on bacteria, Dr. Déziel said, "Cranberry PACs interrupt the ability for bacteria to communicate with each other, spread and become virulent -- a process known as quorum sensing. The cranberry extract successfully interferes with the chain of events associated with the spread and severity of chronic bacterial infections."

Added to the evidence of cranberry's role in preventing recurrent urinary tract infections by blocking bacteria from sticking to cell walls, the current study suggests that PACs may help control the virulence or spread of potentially dangerous bacterial infections around the world.

New drug appears to decrease inflammation in the brain linked to Alzheimer's disease

An experimental drug shows promise in treating Alzheimer's disease by preventing inflammation and removing abnormal protein clumps in the brain that are associated with the disease, suggests a study in mice presented at the ANESTHESIOLOGY® 2016 annual meeting.

A key characteristic of Alzheimer's disease is the development of abnormal protein clumps called amyloid plaques and tangled bundles of fibers in the brain. These changes cause inflammation in the brain and damage to the neurons. This progressive damage leads to memory loss, confusion and dementia. The new drug, known as NTRX-07, appears to decrease this inflammation in the brain, while preserving neurons and regenerative cells in the brain.

"This drug may reduce inflammation in the brain, which is linked to Alzheimer's disease," said lead researcher Mohamed Naguib, M.D., a physician anesthesiologist in the Department of General Anesthesiology at the Cleveland Clinic and professor of anesthesiology at the Cleveland Clinic Lerner College of Medicine. "NTRX-07 uses a different mechanism than many other Alzheimer's drugs currently available, as it targets the cause of the disease, not just the symptoms."

The authors discovered NTRX -07's memory-restoring abilities while studying the drug's potential to treat a complex, chronic pain condition called neuropathic pain. "Patients who have neuropathic pain have chronic neuroinflammation," said Dr. Naguib. "This is a compound that blunts that inflammation."

Researchers tested NTRX -07 on mice bred to have similar brain neurodegenerative issues as seen in Alzheimer's. They found that inflammation produced in response to the disease caused changes in the brain's microglia cells - immune cells that typically remove dangerous amyloid plaques (protein clumps) in the brain. As the amyloid plaques accumulated in the mice, the microglia (immune cells) were unable to remove them, leading to inflammation and damage to nerve cells, which caused decreased cognitive ability.

Microglia cells have receptors on the surface called CB2 receptors, which when activated can produce an anti-inflammatory response. NTRX -07 targets CB2 receptors, which leads to decreased inflammation and prevents damage to the brain tissue. The new drug improved removal of abnormal amyloid plaques and improved memory performance and other cognitive skills.

The drug also increased levels of a protein called SOX2, which has been shown to help new brain cells develop and protect the brain in people with Alzheimer's disease. The study found in mice treated with NTRX-07, the levels of SOX2 were restored to normal levels. In contrast, mice treated with a placebo showed decreased levels of SOX2, active inflammation in the brain, poor removal of amyloid plaques, and poor memory performance.

FDA approves new therapy for initial treatment of soft tissue sarcoma

In continuation of my update on Doxorubicin

The U.S. Food and Drug Administration today granted accelerated approval to Lartruvo (olaratumab) with doxorubicin to treat adults with certain types of soft tissue sarcoma (STS), which are cancers that develop in muscles, fat, tendons or other soft tissues. Lartruvo is approved for use with the FDA-approved chemotherapy drug doxorubicin for the treatment of patients with STS who cannot be cured with radiation or surgery and who have a type of STS for which an anthracycline (chemotherapy) is an appropriate treatment.

"For these patients, Lartruvo, added to doxorubicin, provides a new treatment option," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and acting director of the FDA's Oncology Center of Excellence. "This is the first new therapy approved by the FDA for the initial treatment of soft tissue sarcoma since doxorubicin's approval more than 40 years ago."

The National Cancer Institute estimates that 12,310 new cases of STS and nearly 5,000 deaths are likely to occur from the disease in 2016. The most common treatment for STS that cannot be removed by surgery is treatment with doxorubicin alone or with other drugs. STS includes a wide variety of tumors arising in the muscle, fat, blood vessels, nerves, tendons or the lining of the joints.

Lartruvo is a platelet-derived growth factor (PDGF) receptor-alpha blocking antibody. When stimulated, PDGF receptors cause tumor growth. Lartruvo works by blocking these receptors, which may help slow or stop tumor growth.

The safety and efficacy of Lartruvo were studied in a randomized clinical trial involving 133 patients with more than 25 different subtypes of metastatic STS. Patients received either Lartruvo with doxorubicin or doxorubicin alone. This trial measured the length of time patients lived after treatment (overall survival), the length of time tumors did not grow after treatment (progression-free survival) and the percentage of patients who experienced shrinkage of their tumors (overall response rate). Patients in this trial who received Lartruvo with doxorubicin had a statistically significant improvement in overall survival: the median survival was 26.5 months compared to 14.7 months for patients who received doxorubicin alone. Patients who received Lartruvo with doxorubicin had a median progression-free survival of 8.2 months compared to 4.4 months for patients who received doxorubicin alone. Tumor shrinkage was 18.2 percent for patients who received Lartruvo with doxorubicin and 7.5 percent for those who received doxorubicin alone.

Lartruvo has serious risks including infusion-related reactions and embryo-fetal harm. Infusion-related reactions include low blood pressure, fever, chills and rash. The most common side effects of treatment with Lartruvo are nausea, fatigue, low levels of white blood cells (neutropenia), musculoskeletal pain, inflammation of the mucous membranes (mucositis), hair loss (alopecia), vomiting, diarrhea, decreased appetite, abdominal pain, nerve damage (neuropathy) and headache.

The FDA granted the Lartruvo application fast track designation, breakthrough therapy designation and priority review status because preliminary clinical evidence indicated that it may offer a substantial improvement in effectiveness in the treatment of a serious or life-threatening disease or condition. The FDA is approving Lartruvo under the agency's accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease or condition based on clinical data showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. The sponsor is conducting a larger study, which is currently underway, to further explore the effectiveness of Lartruvo across the multiple subtypes of STS.

Lartruvo also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs intended to treat rare diseases.