Maple syrup makes disease-causing bacteria more susceptible to antibiotics, study shows

A concentrated extract of maple syrup makes disease-causing bacteria more susceptible to antibiotics, according to laboratory experiments by researchers at McGill University.

The findings, which will be published in the journal Applied and Environmental Microbiology, suggest that combining maple syrup extract with common antibiotics could increase the microbes' susceptibility, leading to lower antibiotic usage. Overuse of antibiotics fuels the emergence of drug-resistant bacteria, which has become a major public-health concern worldwide. Prof. Nathalie Tufenkji's research team in McGill's Department of Chemical Engineering prepared a concentrated extract of maple syrup that consists mainly of phenolic compounds. Maple syrup, made by concentrating the sap from North American maple trees, is a rich source of phenolic compounds.

Maple syrup makes disease-causing bacteria more susceptible to antibiotics, study shows 

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

In continuation of my update on Ibrutinib

 

We know that, Ibrutinib   also known as PCI-32765 and marketed under the name Imbruvica) is an anticancer drug targeting B-cell malignancies. It was approved by the US FDA in November 2013 for the treatment of mantle cell lymphoma and in February 2014 for the treatment of chronic  lymphocytic leukemia  It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase (BTK)  Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson'sJanssen Pharmaceutical division for additional B-cell malignancies including diffuse large B-cell lymphoma and multiple myeloma

--------------------

Now.....

The most recent results from a clinical trial show that ibrutinib, a newly approved drug for Waldenstrom's Macroglobulinemia, continued to control the rare blood cancer, with 95 percent of patients surviving for two years, report investigators from Dana-Farber Cancer Institute.

The median overall response rate was 91 percent after a median of 19 months of treatment, and in 69 percent of patients the cancer had not worsened two years after beginning treatment. When the cancer did progress, it began at a median time of 9.6 months after the start of treatment. The results are reported in The New England Journal of Medicine.

An earlier analysis of data from this phase 2 multicenter study supported the Food and Drug Administration's approval in January of ibrutinib as the first and only treatment for Waldenstrom's, a rare form of lymphoma that affects about 1,500 people annually in the United States.

"These findings herald a new era for the treatment of Waldenstrom's Macroglobulinemia, and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies," said first author Steven Treon, MD, PhD, director of the Bing Center for Waldenstrom's Macroglobulinemia at Dana-Farber.

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

New herbal tea to treat malaria in Africa

Malaria is a critical health problem in West Africa, where traditional medicine is commonly used alongside modern healthcare practices. An herbal remedy derived from the roots of a weed, which was traditionally used to alleviate malarial symptoms, was combined with leaves and aerial portions from two other plants with antimalarial activity, formulated as a tea, and eventually licensed and sold as an antimalarial phytomedicine. The fascinating story and challenges behind the development of this plant-based treatment are presented in The Journal of Alternative and Complementary Medicine, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on The Journal of Alternative and Complementary Medicinewebsite until May 14, 2015.

Dr. Merlin Willcox (University of Oxford, U.K.), Dr. Zéphirin Dakuyo (Phytofla, Banfora, Burkina Faso), and coauthors discuss the antimalarial and pharmacological properties of the herbal medication derived from Cochlospermum planchonii 

(a shrubby weed known as N'Dribala), Phyllanthus amarus,  

and Cassia alata. 

The authors provide a unique historical perspective in describing the early evaluation, development, and production of this phytomedicine. They present the ongoing research and challenges in scaling up cultivation and harvesting of the plants and in production of the final product. The article also describes other traditional uses of the medication, such as to treat hepatitis.

Ref : http://online.liebertpub.com/doi/full/10.1089/acm.2014.0147

New herbal tea to treat malaria in Africa

Itraconazole drug shows potential in cancer treatment

In continuation of my update on Itraconazole

Anti-fungal drug shows promise as potential new cancer treatment.A common anti-fungal treatment has joined the ranks of drugs that may be suitable for use in treating cancer, according to research from the Repurposing Drugs in Oncology (ReDO) project published in ecancermedicalscience.  

The ReDO project is an international collaboration of anticancer researchers dedicated to promoting the cause of common medicines which may represent an untapped source of novel therapies for cancer.

In partnership with ecancer, the ReDO project is publishing a series of papers on drugs that have enough clinical evidence to be taken to clinical trials.Itraconazole is a drug used to treat a broad range of fungal infections, including skin and nail infections.

It also has a lot of potential as a new cancer treatment, according to the ReDo project.

"Itraconazole shows potential in a number of areas with high unmet patient needs, particularly in non-small cell lung cancer and possibly in some rarer malignancies," says Pan Pantziarka, PhD, member of the ReDO project and the Anticancer Fund.

Itraconazole drug shows potential in cancer treatment

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Effimune announced today that it had received the authorization from the Belgian regulatory authority, the FAMHP (Federal Agency for Medicines and Health Products) for a Phase I clinical trial of FR104, its drug candidate for controlling the regulation of the immune system.

This double-blind randomized clinical trial will take place on 70 healthy volunteers (both men and women) over a period of 9 months, and will prepare the future development of FR104 in rheumatoid arthritis and kidney transplantation. The primary objectives of the trial are to establish the safety and tolerability of FR104 and assess its pharmacodynamics and pharmacokinetics. Since September 2013, FR104 has been under a global license agreement with Janssen Biotech, Inc., a subsidiary of Johnson & Johnson.

Benzoic acid, 2,3,4,5-tetrachloro-6-(2, 4,5,7-tetrabromo-6-hydroxy-3-oxo-3H-xanthen-9-yl) -

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Wilson Therapeutics' WTX101-201 Phase 2 clinical study to be presented at EASL annual meeting

Bis-choline tetrathiomolybdate, or WTX101, is a salt of tetrathiomolybdate (TTM, MoS₄²⁻) and choline currently under investigation as a therapy against Wilson's disease, a rare and potentially fatal disease in which the body cannot regulate copper. Wilson disease is an autosomal recessive genetic disorder that is manifested by serious hepatic, neurologic or psychiatric symptoms. The disease is fatal if left undiagnosed and untreated. It is estimated that approximately 1 individual in every 15,000 worldwide have Wilson's disease, corresponding to approximately 30,000 individuals in the European Union and approximately 20,000 in the United States.

Bionomics to present BNC105 trial results of metastatic renal cancer at Asian Oncology Summit

The data identify ferritin and IL-8 as two baseline biomarkers that correlate with an improved progression free survival (PFS) in patients. Eighty nine percent of patients expressing higher plasma levels of ferritin and lower plasma levels of IL-8 at baseline were disease progression-free at six months. The data show that biomarker-based patient selection has the potential to optimise clinical outcomes in the treatment of renal cancer. There are 6.3 new cases of renal cancer and 1.7 deaths per 100,000 people in Asia each year.

BNC105 is a novel compound being developed as a vascular disrupting agent (VDA) for the treatment of cancer. VDAs are drugs that disrupt the blood vessels that nourish tumours. This approach has a number of advantages over classical chemotherapy, including stronger impact on tumour cell death, applicability to a wider variety of cancers, and lowered risk of the emergence of therapy-resistant tumour cells.

More...

Bionomics to present BNC105 trial results of metastatic renal cancer at Asian Oncology Summit

New combination therapy holds promise for treating HER2-positive breast cancer

Resistance to therapy is a major problem in the cancer field. Even when a treatment initially works, the tumors often find ways around the therapy. Using human cell lines of the HER2-positive breast cancer subtype, researchers from the UNC School of Medicine and UNC Lineberger Comprehensive Cancer Center have detailed the surprising ways in which resistance manifests and how to defeat it before it happens.

The discovery, published today in the journal CELL Reports, provides the experimental evidence for the potential development of a novel combination therapy for HER2-positive breast cancer. The combination includes the FDA approved drug lapatinib (right structure) and a new experimental drug called a BET bromodomain inhibitor -JQ1 (see structure left), which works by disrupting the expression of specific genes.

 

This study, a collaboration of 20 University of North Carolina researchers, is the first time a BET bromodomain inhibitor has been shown to prevent the onset of resistance to drugs such as lapatinib in breast cancer cells.

"This research was done in cell lines of human HER2-positive breast cancer, not in patients; but the results are very striking," said Gary Johnson, PhD, Kenan Distinguished Professor and chair of the department of pharmacology, member of the UNC Lineberger Comprehensive Cancer Center, and senior author of the paper. "The combination treatments are currently being tested in different mouse models of breast cancer. Our goal is to create a new kind of therapy that could help oncologists make the response to treatment more durable and lasting for breast cancer patients."

Ref : http://www.nature.com/nature/journal/v468/n7327/abs/nature09504.html

New combination therapy holds promise for treating HER2-positive breast cancer

New high-throughput screening method may uncover novel treatments for kidney disease .

CKD affects more than 13% of adults in the United States, with diabetes, hypertension and atherosclerosis being common risk factors. Most patients rely on antihypertensive medications for treatment, and there are no therapies available that directly and specifically target the kidney.

A team led by Vineet Gupta, PhD and Jochen Reiser, MD, PhD (Rush University Medical Center) has now developed a system that can be used to identify novel drug candidates that protect the function of kidney podocytes, cells that are critical for filtering the blood. Damage to these cells is a hallmark of CKD.

"A key barrier to the rational development of podocyte-directed therapeutics has been a lack of cell-based assays for use in high-throughput drug discovery environment," said Dr. Gupta. "Our report describes what we believe to be the  first  podocyte  cell-based highcontent screening assay for the identification of novel podocyte-directed therapeutics in a high-throughput fashion."

Using the assay, which analyzes thousands of podocytes under different conditions in multi-well plates, the investigators identified 24 small molecules that protected podocytes against injury. When they treated mice and rats with one   of  the  molecules, called   pyrintegrin, the
animals' podocytes remained healthy despite being exposed to damaging agents.Pyrintegrin activates β1 integrin, a protein that acts as a molecular bridge to help podocytes hold onto the outside of blood vessels and maintain the filtration apparatus in the kidney.

"We believe that this assay could provide the much needed boost in fueling the discovery and development of kidney directed therapeutics, development of which has significantly lacked in recent times," said Dr. Reiser.

Ref : http://jasn.asnjournals.org/content/early/2015/04/09/ASN.2014090859

New high-throughput screening method may uncover novel treatments for kidney disease -- 

Allergy drug inhibits hepatitis C in mice

Chlorcyclizine (Di-Paralene,  Mantadil, Pruresidine, Trihistan) is a first-generation antihistamine of the phenylpiperazine class marketed in the United States and certain other countries. It is used primarily to treat allergy symptoms such as rhinitis,urticaria, and pruritus, and may also be used as an antiemetic. In addition to its antihistamine effects, chlorcyclizine also has some anticholinergic, antiserotonergic, and local anesthetic properties. It also has been studied as a potential treatment forhepatitis C.

The hepatitis C virus (HCV) causes liver inflammation and often leads to serious complications such as cirrhosis. Early diagnosis and treatment of HCV can prevent liver damage. Drugs are available to treat HCV, but costs can reach tens of thousands of dollars.

"Although hepatitis C is curable, there is an unmet need for effective and affordable medication," said lead author T. Jake Liang, M.D., senior investigator at NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "CCZ is a promising candidate for part of a treatment regimen for this potentially life-threatening disease."

Conducted at the NIH campus in Bethesda, Maryland, the study found that CCZ blocked the early stage of HCV infection likely by impairing the ability of the virus to enter human liver cells grafted in the mice. The outcome was similar to that of commonly used antiviral drugs but without those drugs' toxic side effects.

"Using an innovative high-throughput screening process, we identified CCZ as a potent inhibitor of hepatitis C," said Anton Simeonov, Ph.D., acting scientific director of NIH's National Center for Advancing Translational Sciences (NCATS), which collaborated in the study. "Identifying already approved drugs from the NCATS Pharmaceutical Collection may offer a faster route to potential discovery of treatments for all diseases."

The researchers will next study how the drug affects people. CCZ is currently used for the treatment of allergies, not for HCV. "People should not take CCZ to treat their hepatitis C until it has been demonstrated that CCZ can be used safely and effectively for that purpose," cautions Liang.

Ref : http://stm.sciencemag.org/content/7/282/282ra49

Allergy drug inhibits hepatitis C in mice  

Enzalutamide: Indication of major added benefit for over 75-year-olds

In continuation of my update on enzalutamide

According to the findings, in comparison with watchful waiting the drug can prolong overall survival and delay the occurrence of disease complications. In men aged 75 years or older, IQWiG sees an indication of a major added benefit. There is also an indication of an added benefit in younger men; however, the extent is rated as "considerable."

Approval study terminated prematurely

The assessment was based on a randomized controlled trial (PREVAIL), which was the approval study for the indication described above. In this study, patients received either enzalutamide or a placebo, while the hormone-blocking medication was continued in all patients. In each study arm, treatment was continued until either the disease worsened (progression) or safety concerns arose, for example, because toxicity was too high.

As the interim analysis planned for the outcome "overall survival" had already shown good efficacy of enzalutamide, this was considered as the final Analysis.

Survival advantage depends on age

The difference in overall survival is statistically significant between the two study arms. However, as the further analysis of the data shows, this advantage is age dependent. It is greater in older men (75 years or more) than in younger ones. In each case, the IQWiG researchers derive an indication of an added benefit from these results, albeit with a different extent (major or minor).

Bone-related complications occur later

The study data also showed relevant group differences in favour of enzalutamide for other outcomes. For instance, bone-related complications occurred later in patients receiving enzalutamide than in those receiving placebo. IQWiG sees an indication of an added benefit here.

In addition, it took longer until opiates were used, that is, severe pain occurred later in patients receiving enzalutamide. This also applies to the occurrence of side effects (severe and serious adverse events) and the discontinuation of treatment due to side effects. Health-related quality of life also deteriorated later.

Enzalutamide: Indication of major added benefit for over 75-year-olds  

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