Nintedanib in lung cancer: Added benefit depends on disease severity

In continuation of my update on Nintedanib

According to the findings, there is an indication of a minor added benefit of nintedanib in combination with docetaxel in patients without brain metastases. However, in patients with brain metastases, the new drug has more disadvantages than chemotherapy with docetaxel alone. This results in a hint of a lesser benefit of nintedanib with the extent "considerable."

Findings from the only study are biased: at most indications can be derived

In its dossier the drug manufacturer compares treatment comprising nintedanib plus docetaxel with treatment comprising placebo plus docetaxel. As the treatment period in the nintedanib arm was longer than in the placebo arm (median: 4.3 versus 3 months), the observation periods for the study arms differed. Except for overall survival, the results are therefore uncertain for all outcomes.

In principle, at most an indication of an added benefit can be derived from the results of the only study included in the manufacturer dossier. As the analysis of the data shows, the advantages or disadvantages of nintedanib in combination with docetaxel primarily depend on whether patients already had brain metastases at the start of the study or not.

Patients without brain metastases live longer

Patients without brain metastases who received nintedanib in combination with docetaxel lived longer than study participants who were only treated with docetaxel (median: 13.5 versus 10.3 months). This results in an indication of a minor added benefit of nintedanib.

Although diarrhoea was more frequent in patients receiving nintedanib, this disadvantage does not challenge the survival advantage. Therefore, overall an indication remains of a minor added benefit for patients without brain metastases.

More symptoms in patients with brain metastases

Nintedanib in lung cancer: Added benefit depends on disease severity  

Pomegranate-date cocktail a day keeps the doctor away

Pomegranate-date cocktail a day keeps the doctor away 

A team of researchers at the Technion-Israel Institute of Technology, led by Professor Michael Aviram of the Rappaport Faculty of Medicine and Rambam Medical Center, has discovered that the combination of pomegranate juice and dates along with their pits provide maximum protection against atherosclerosis (plaque buildup or hardening of the arteries), which can cause a heart attack or stroke. The findings were published in the most recent issue (March 26, 2015) ofFood & Function, a journal of The Royal Society of Chemistry.

A number of risk factors are involved in the development of atherosclerosis, including cholesterol oxidation, which leads to accumulation of lipids in the arterial wall. Natural antioxidants can slow down the oxidation process in the body, and serve to reduce the risk of heart attack. For the past 25 years, Prof. Aviram and his research team have been working on isolating and researching those antioxidants, in order to keep plaque buildup at bay.

Going into the most recent study, the team was aware of the individual benefits provided by pomegranates and dates. Pomegranate juice, rich in polyphenolic antioxidants (derived from plants), has been shown to most significantly reduce oxidative stress. Dates, which are rich sources of phenolic radical scavenger antioxidants, also inhibit the oxidation of LDL (the so-called "bad cholesterol") and stimulate the removal of cholesterol from lipid-laden arterial cells. Prof. Aviram had a hunch that since dates and pomegranate juice are composed of different phenolic antioxidants, the combination could thus prove more beneficial than the sum of its parts.

In a trial performed on arterial cells in culture, as well as in atherosclerotic mice, the Technion team found that the triple combination of pomegranate juice, date fruits and date pits did indeed provide maximum protection against the development of atherosclerosis because the combination reduced oxidative stress in the arterial wall by 33% and decreased arterial cholesterol content by 28%.

The researchers conclude that people at high risk for cardiovascular diseases, as well as healthy individuals, could benefit from consuming the combination of half a glass of pomegranate juice (4 ounces), together with 3 dates. Ideally, the pits should be ground up into a paste and eaten as well, but even without the pits, the combination is better than either fruit alone.

Ref : http://pubs.rsc.org/en/Content/ArticleLanding/2015/FO/C4FO00998C#!divAbstract

Study on new treatment for prostate cancer

A new study represents the first time LTPs have been applied on cells grown directly from patient tissue samples. Taking both healthy prostate cells and prostate cancer tissue cells from a single patient, the study allowed for direct comparison of the effectiveness of the treatment. Scientists discovered that LTPs may be a potential option for treatment of patients with organ confined prostate cancer, and a viable, more cost-effective alternative to current radiotherapy and photodynamic therapy (PDT) treatments.

Study on new treatment for prostate cancer  

Ref : http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2015113a.html

Enriched broccoli reduces cholesterol

In continuation of my update on broccoli

Including a new broccoli variety in the diet reduces blood LDL-cholesterol levels by around 6 percent, according to the results of human trials. The broccoli variety was bred to contain two to three times more of a naturally occurring compound glucoraphanin. It is now available in supermarkets in England, under the name Beneforte.

The broccoli variety was bred to contain two to three times more of a naturally occurring compound glucoraphanin. It is now available in supermarkets, under the name Beneforte.

Working with colleagues at the University of Reading, in two independent studies, the researchers gave a total of 130 volunteers 400g of the high glucoraphanin broccoli per week to include in their normal diet.

After 12 weeks, they saw the levels of LDL-cholesterol in their blood drop by an average of about 6%. Elevated LDL cholesterol is a recognised risk factor for heart disease. Although the reduction seen in these trials is small, at a population level, a 1% reduction in LDL-cholesterol has been associated with a 1-2% reduction in risk of coronary artery disease.

Glucoraphanin is thought to work by helping our bodies retune cellular metabolism. Mitochondria, the energy centres of the cell, convert sugars and fats into energy. But if they aren't working efficiently, or if we overload them with too much fat or sugar, one response is to channel excess into cholesterol.

Glucoraphanin is converted in the body to sulphoraphane, which turns on specific genes that activate our bodies' defences against this happening, rebalancing metabolism away from the production of LDL cholesterol. This new study, published in the journal Molecular Nutrition and Food Research, provides the evidence for this reduction.

High glucoraphanin Beneforté broccoli was developed using traditional breeding techniques at IFR's partners on the Norwich Research Park, the John Innes Centre and the University of East Anglia, and Seminis Vegetable Seeds Inc.

This study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), Innovate UK and Seminis Vegetable Seeds Inc.

Other foods or ingredients that have been proven to lower LDL-cholesterol are beta-glucans in oats and plant stanols. These work by reducing cholesterol absorption into the body. As glucoraphanin works by reducing how much our bodies make, eating these foods together is likely to have an additive effect.

Enriched broccoli reduces cholesterol 

Journal of Drugs in Dermatology publishes findings on new injectable drug ATX-101

In continuation of my update on ATX-101    .......

Double chins are clinically defined by accumulation of subcutaneous fat in the submental area. The result? A double chin that impacts perceptions of facial attractiveness. In "A Phase I Safety and Pharmacokinetic Study of ATX-101: Injectable, Synthetic Deoxycholic Acid for Submental Contouring," Patricia Walker MD PhD, Jere Fellmann PhD, and Paul F. Lizzul MD PhD MBA MPH explain how ATX-101 (deoxycholic acid [DCA] injection) has the potential to provide a less invasive alternative for submental fat reduction and contouring. Both in vivo and in vitro studies show that, when injected into submental subcutaneous fat tissue, ATX-101 results in the targeted destruction of fat cells. The data support favorable safety and efficacy observations. Adverse events were bruising and swelling associated with the treatment area that are mild or moderate in severity. FDA approval for use of ATX-101 above the chest is expected in May 2015.

Journal of Drugs in Dermatology publishes findings on new injectable drug ATX-101

Low doses of imatinib drug can push immune system to combat bacterial infections

In contiuation of my update on Imatinib

Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory researchers have found.

The results were published March 30, 2015 in the journal PLOS Pathogens.

The findings suggest imatinib, known commercially as Gleevec , or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cells in vitro, but provides information on how to dose imatinib for new clinical applications.

"We think that low doses of imatinib are mimicking 'emergency hematopoiesis,' a normal early response to infection," says senior author Daniel Kalman, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.

Ref : http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004770

Low doses of imatinib drug can push immune system to combat bacterial infections

Old leukemia drug may help in fight against cancer

A drug used for decades to treat leukemia may have other uses in the fight against cancer, researchers at the University of Missouri have found. Previously, doctors used 6-Thioguanine, or 6-TG, as a chemotherapy treatment to kill cancer cells in patients with leukemia.

Old leukemia drug may help in fight against cancer

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

Pharmalink AB, a specialty pharma company, announces that it has acquired a novel product candidate in development for treating inflammation from Synartro AB. No financial details are disclosed.

The product candidate, which consists of an anti-inflammatory drug conjugated to a biopolymer, has been developed using Synartro's drug delivery technology to create locally acting pharmaceuticals with limited systemic exposure. Pharmalink intends to develop the product for osteoarthritis, an indication where it has demonstrated promising results in pre-clinical studies. Pharmalink will apply its formulation and clinical development expertise to advance the candidate product through clinical trials towards market.

 

Pharmalink has extensive experience in developing locally delivered anti-inflammatory drugs with limited systemic uptake. Its most advanced product is Nefecon®, (a new oral formulation of the glucocorticosteroid, budesonide above structures respectively), modified-release capsule of the corticosteroid, budesonide, in Phase 2b clinical development for treating patients with IgA nephropathy at risk of developing end-stage renal disease, despite optimized standard-of-care therapy.

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

Novel molecule inhibits cancer-causing transcription factors

A novel molecule designed by scientists at the University of Massachusetts Medical School and the University of Virginia inhibits progression of a hard-to-treat form of recurring acute myeloid leukemia (AML) in patient tissue. The small molecule is one of the first designed to specifically target a cancer-causing transcription factor. Previously thought to be an undruggable target, this strategy may be used to design other novel molecules that can specifically inhibit cancer-causing transcription factors. Details of the work were published in Science.

Transcription factors are single- or multi-protein complexes that regulate transcription of DNA into messenger RNA and gene expression by binding to regions on the genome next to a gene. Mutations in transcription factors can result in altered gene expression programs that give way to new, cancer-causing functions. Although these aberrant transcription factors are promising targets for new therapeutics, the complexity of interrupting very specific protein-to-protein interactions has made it difficult to find small molecules or design drugs that treat these cancers.

"When we look at inhibitors, they usually target an enzyme or receptor. There aren't a lot of good examples of transcription factor inhibitors in clinical trials," said Lucio H. Castilla, PhD, associate professor of molecular, cell and cancer biology and co-leader of the study. "Here, we've used our extensive knowledge of a mutant transcription factor found in a subset for acute myeloid leukemia patients to design a molecule that can specifically sequester only the oncogenic mutant. This leaves the normal transcription factor to bind to the DNA and restore gene expression.".......

Ref : http://www.sciencemag.org/content/347/6223/779.abstract?sid=73b04258-783e-43e4-8e1d-09fe5eb7d331

Novel molecule inhibits cancer-causing transcription factors

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

Pharmalink AB, a specialty pharma company, announces that it has acquired a novel product candidate in development for treating inflammation from Synartro AB. No financial details are disclosed.

The product candidate, which consists of an anti-inflammatory drug conjugated to a biopolymer, has been developed using Synartro's drug delivery technology to create locally acting pharmaceuticals with limited systemic exposure. Pharmalink intends to develop the product for osteoarthritis, an indication where it has demonstrated promising results in pre-clinical studies. Pharmalink will apply its formulation and clinical development expertise to advance the candidate product through clinical trials towards market.

 

Pharmalink has extensive experience in developing locally delivered anti-inflammatory drugs with limited systemic uptake. Its most advanced product is Nefecon®, (a new oral formulation of the glucocorticosteroid, budesonide above structures respectively), modified-release capsule of the corticosteroid, budesonide, in Phase 2b clinical development for treating patients with IgA nephropathy at risk of developing end-stage renal disease, despite optimized standard-of-care therapy.

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

GFT505 demonstrates dose-dependent efficacy on primary endpoint in phase 2 NASH trial

GENFIT (Euronext: GNFT; ISIN: FR0004163111), today announces topline results of the phase 2 GOLDEN-505 trial in NASH.

Due to the unexpected rate of resolution of NASH in patients randomized to placebo who had early NASH (NAS of 3, placebo response rate>57%), along with the high number of sites for a limited sample size, the study as initially designed did not enable the trial to meet directly the primary endpoint. With correction for this baseline severity and site heterogeneity by a standardized statistical analysis, GFT505 120mg meets the primary endpoint: Reversal on NASH without worsening of fibrosis, as detailed below.

Treatment with GFT505 provides a significant beneficial effect on the primary endpoint (GFT505 120mg vs placebo, p=0.016, RR=2.03) in the global randomized population (n=274, full analysis set), where patients without an end of treatment biopsy were considered as non-responders. The primary endpoint was also achieved in the evaluable population of patients who underwent both baseline and end of study liver biopsies (n=237, ITT; p=0.027 vs placebo; RR=1.94). In the evaluable patient population, GFT505 120mg also has a beneficial effect of a decrease of NAS-score ≥2 (p=0.04 vs placebo).

Early NASH patients with NAS=3 were not included in other recent NASH trials. If the same is done in the GOLDEN-505 study, keeping patients with more severe disease defined by NAS≥4 (n=202), GFT505 120mg demonstrates a doubling of responders on the primary endpoint (22.4% vs 12.7%, p=0.046, RR=1.9), thus providing evidence of a clinically meaningful benefit in patients with more advanced disease.

GFT505 demonstrates dose-dependent efficacy on primary endpoint in phase 2 NASH trial

Anti-diabetic medication activates brain sensors, promotes weight gain

Medication used to treat patients with type II diabetes activates sensors on brain cells that increase hunger, causing people taking this drug to gain more body fat, according to researchers at Georgia State University, Oregon Health and Science University, Georgia Regents University and Charlie Norwood Veterans Administration Medical Center.

The study, published on March 18 in The Journal of Neuroscience, describes a new way to affect hunger in the brain and helps to explain why people taking a class of drugs for type II diabetes gain more body fat.

Type II diabetes, the most common form of diabetes, affects 95 percent of diabetes sufferers. People with type I or type II diabetes have too much glucose, or sugar, in their blood. Type II diabetes develops most often in middle-aged and older adults and people who are overweight and inactive, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

The research team found that sensors in the brain that detect free circulating energy and help use sugars are located on brain cells that control eating behavior. This is important because many people with type II diabetes are taking antidiabetics, known as thiazolidinediones (TZDs), which specifically activate these sensors, said Johnny Garretson, study author and doctoral student in the Neuroscience Institute and Center for Obesity Reversal at Georgia State.

The study found peroxisome proliferator-activated receptor ϒ (PPARϒ) sensors on hunger-stimulating cells, known as agouti-related protein (AgRP) cells, at the base of the brain in the hypothalamus. Activating these PPARϒ sensors triggers food hoarding, food intake and the production of more AgRP. When AgRP cells are activated, animals become immediately hungry. These cells are so potent they will wake a rodent up from slumber to go eat, Garretson said.

TZDs help to treat insulin resistance, in which the body doesn't use insulin the way that it should. They help the body's insulin work properly, making blood glucose levels stay on target and allowing cells to get the energy they need, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

Anti-diabetic medication activates brain sensors, promotes weight gain

Promising drug a 'new paradigm' for treating leukemia

Researchers at the University of Virginia School of Medicine have developed a compound that delays leukemia in mice and effectively kills leukemia cells in human tissue samples, raising hopes that the drug could lead to improved treatments in people. The researchers call it an exciting "new paradigm" for treating leukemia.

The compound works by disabling an altered cellular protein that drives one type of acute myeloid leukemia, the most common form of adult leukemia. By blocking that protein, the drug allows a cancerous cell to detect that it has problems and die, rather than continue to grow and spread. In essence, the compound blocks the cellular machinery that the cancer has highjacked.

"This drug that we've developed is ... targeting a class of proteins that hasn't been targeted for drug development very much in the past. It's really a new paradigm, a new approach to try to treat these diseases," said researcher John H. Bushweller, PhD, of the UVA Department of Molecular Physiology and Biological Physics. "This class of proteins is very important for determining how much of many other proteins are made, so it's a unique way of changing the way the cell behaves."

The drug is notable because of its specificity, killing cancerous cells but not healthy cells. "It's what we call a targeted agent. It hits one specific protein," Bushweller said. "It's not a killer of many other types of cells. As far as we can tell, it only really kills the leukemia cells that have this particular altered protein in them."

Ref : http://www.sciencemag.org/content/347/6223/779

Promising drug a 'new paradigm' for treating leukemia  

Common bacteria on verge of becoming antibiotic-resistant superbugs

Antibiotic resistance is poised to spread globally among bacteria frequently implicated in respiratory and urinary infections in hospital settings, according to new research at Washington University School of Medicine in St. Louis.

The study shows that two genes that confer resistance against a particularly strong class of antibiotics can be shared easily among a family of bacteria responsible for a significant portion of hospital-associated infections.

Drug-resistant germs in the same family of bacteria recently infected several patients at two Los Angeles hospitals. The infections have been linked to medical scopes believed to have been contaminated with bacteria that can resist carbapenems, potent antibiotics that are supposed to be used only in gravely ill patients or those infected by resistant bacteria.

"Carbapenems are one of our last resorts for treating bacterial infections, what we use when nothing else works," said senior author Gautam Dantas, PhD, associate professor of pathology and immunology. "Given what we know now, I don't think it's overstating the case to say that for certain types of infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we rely on to treat bacterial infections are no longer effective."

Dantas and other experts recommend strictly limiting the usage of carbapenems to cases in which no other treatments can help.

The study, conducted by researchers at Washington University, Barnes-Jewish Hospital and the National University of Sciences and Technology in Pakistan, is available online in Emerging Infectious Diseases.

The researchers studied a family of bacteria called Enterobacteriaceae, which includes E. coli, Klebsiella pneumoniae and Enterobacter. Some strains of these bacteria do not cause illness and can help keep the body healthy. But in people with weakened immune systems, infections with carbapenem-resistant versions of these bacteria can be deadly.

Common bacteria on verge of becoming antibiotic-resistant superbugs 

New drug fails to prevent irreversible injury to the heart after angioplasty

Patients who received the new drug Bendavia before undergoing angioplasty or receiving a stent to clear blocked arteries after a heart attack showed no significant reduction in scarring as compared to patients given a placebo, according to a study presented at the American College of Cardiology's 64th Annual Scientific Session.

The study is the first randomized, controlled trial of Bendavia, a drug designed to reduce the extent of tissue damage in the heart through a new approach that targets mitochondria in the cells. Although patients receiving the drug showed a 10 percent reduction in scarring during the first three days after surgery as measured by the levels of an enzyme called creatinine kinase-MB, the study's primary endpoint, the difference was not statistically significant. The results also suggested a trend toward improved heart pumping function during the eight hours following the drug's administration, but that trend also did not reach statistical significance.

New drug fails to prevent irreversible injury to the heart after angioplasty