Adult cancer drugs show promise against an aggressive childhood brain tumor

Researchers relied on mice with group 3 medulloblastoma grown from patient tumors. The mice were developed in Roussel’s laboratory and are a powerful tool for testing the effectiveness of drugs against human tumors. Researchers used the mice to show that pemetrexed and gemcitabine worked against human group 3 tumors and that the drugs could be used in combination with existing chemotherapy agents to boost treatment effectiveness without undue risk. Cisplatin and cyclophosphamide were the other drugs used in this study.

“The finding provides a strong rationale for combination therapy with pemetrexed and gemcitabine for treatment of group 3 medulloblastoma,” Roussel said. Researchers found no evidence that mouse tumor cells develop resistance to the drugs.

Pemetrexed works by disrupting the ability of cancer cells to proliferate. Gemcitabine kills cells by triggering their suicide pathway. Researchers also found evidence the drugs work specifically against group 3 medulloblastoma. The drugs did not extend survival of mice with a different medulloblastoma subtype.

The study builds on previous St. Jude research that has helped to revolutionize understanding of the origins of medulloblastoma and laid the foundation for a new era of risk-based therapy. The goal is to maximize the likelihood of a cure and minimize long-term side effects. The approach combines clinical factors and the molecular markers associated with the different medulloblastoma subtypes to guide how radiation and chemotherapy are combined with surgery.

Adult cancer drugs show promise against an aggressive childhood brain tumor  

New combination drug therapy proves very effective in hepatitis C treatments

A new 12-week single tablet regimen of ledipasvir and sofosbuvir have proven to be highly effective in treating a broad range of patients with HCV genotype 1, a form of the virus found in up to 75 percent of infections, according to results unveiled today at the European Association for the Study of the Liver and published simultaneously online by the New England Journal of Medicine.

Between 94 percent and 99 percent of patients were cured of hepatitis C and results were similar in patients who have never been treated and for those who had previously been treated with a combination of peginterferon and ribavirin, the current course that carries sometimes significant side effects.

“Eliminating interferon and ribavirin from treatment regimens is expected to reduce the incidence and severity of adverse events, to simplify the treatment of patients with HCV infection and to provide an option for patients who are ineligible for the current interferon-based treatments,” said Nezam Afdhal, MD, the senior author of the studies, Director of the Liver Center at Beth Israel Deaconess Medical Center and a Professor of Medicine at Harvard Medical School.

Hepatitis C is an infectious disease primarily affecting the liver and which can lead to scarring and cirrhosis and is transmitted primarily through blood transfusions (prior to 1991), intravenous drug use, poorly sterilized medical equipment and sexual transmission.. After exposure 80 percent of patients develop a chronic hepatitis which can lead to cirrhosis, liver failure and liver cancer and hepatitis C is the most common cause for liver transplantation in the US.

Prior treatments have been with interferon which is an injectable cytokine released in response to viral infections. Interferon is combined with other antiviral agents and needs to be used for up to 48 weeks to cure hepatitis C. but is associated with number of side effects, including influenza-like symptoms depression and anemia. Many patients are ineligible for these interferon-based therapies.

“The real advances seen in the Ion trials is that the sofosbuvir-ledipasvir combination tablet enables us to treat almost all genotype 1 patients with a short duration of 8-12 weeks of treatment expanding the treatment pool and increasing the overall cure rate,” said Afdhal.

New combination drug therapy proves very effective in hepatitis C treatments

Statins could ease coughing in lung disease patients, study finds -- ScienceDaily

In continuation of my update on Statins

Common cholesterol-lowering drugs could provide relief to patients suffering from a chronic lung disease, a study has shown. The drugs -- known as statins -- were found to help alleviate the chronic coughing associated with the disease for some patients.

Statins could ease coughing in lung disease patients, study finds 

Researchers develop new eco repellent that stops mosquitoes from attacking humans

Researchers develop new eco repellent that stops mosquitoes from attacking humans

In the battle against malaria researchers at the University of Neuchâtel (Switzerland) have developed a new eco repellent that stops mosquitoes from attacking humans. A new mixture of extracted essential oils seems to be as effective in keeping off mosquitoes as common repellents like Deet for example. The advantage of the new substance: it is fully biodegradable and therefore comes also with fewer side effects.

The Swiss scientists who were conducting their studies within the European research project “ENAROMaTIC” are convinced that their discovery is just the beginning of a new wave of breakthroughs in this field. In the future, natural extracts of essential oils could play an important role in limiting the number of victims caused by disease-carrying insect vectors.

Research produces strong evidence for new class of antidepressant drugs | The University of Manchester

Galanin is a neuropeptide (a small protein) that was discovered and investigated over 30 years ago by various groups including the Swedish scientist Tomas Hokfelt. He is one of the senior authors of the paper published in the journal PNAS.

Professor Hokfelt and others made the fundamental discovery that neurones can release peptides alongside their classical transmitters and that galanin and noradrenaline are one such pair. Both have long been implicated in pain and stress and therefore depression but in the past it had been difficult to study peptides in humans.

The new research by scientists from Sweden, Hungary and the UK demonstrates that galanin is an important stress mechanism in the human brain that influences how sensitive or resilient people are to psychosocial stress.

Lead author Gabriella Juhasz, who is a Research Fellow at the University of Manchester and the Semmelweis University in Budapest, said: “Our research shows that some versions of the gene coding for galanin protect against the risk of depression and anxiety but only in people who have experienced early life neglect or trauma, or recent adverse events.

“Furthermore, the three genes for the three receptors through which galanin acts also influence the risk of depression in people experiencing early or recent life adversity. Crucially, all the galanin related genes are widely separated on different chromosomes and the odds are stacked against four random genes acting in the same way by chance.”

Results from the research indicate that although the results are statistically reliable, galanin effects modify the substantial effects of stress by only a few percent. Indeed the moderate overall genetic influence (about 35%) on depression is likely to be mediated by many small genetic effects interacting with each other and with psychosocial factors converging on stress mechanism in brain.

Co-author Professor Bill Deakin, from the University of Manchester, said: “The findings provide a strong reason to develop drugs that modify galanin functioning as a new class of antidepressant drug. And new drugs are badly needed as almost all commonly prescribed antidepressants act on serotonin and they are often not very effective.

“Our research confirms what previous reports have shown about the variation in the serotonin ‘transporter’ gene and how it influences the risk of depression. We found that the galanin effects are substantially greater than the effects of serotonin.”

Research produces strong evidence for new class of antidepressant drugs | The University of Manchester

New era of lung cancer therapy close to dawning

New era of lung cancer therapy close to dawning

Researchers develop potentially safer and more cost-effective therapeutics against West Nile virus

An international research group led by Arizona State University professor Qiang "Shawn" Chen has developed a new generation of potentially safer and more cost-effective therapeutics against West Nile virus and other pathogens.

The therapeutics, known as monoclonal antibodies (MAbs), and their derivatives were shown to neutralize and protect mice against a lethal dose challenge of West Nile virus - even as late as four days after the initial infection.

"The overarching goal of our research is to create an innovative, yet sustainable and accessible low-cost solution to combat the global threat of West Nile virus," said Chen, a researcher at Arizona State University's Biodesign Institute.

West Nile virus is spread by infected mosquitoes, and targets the central nervous system. It can be a serious, life-altering and even fatal disease, and currently, there is no cure or drug treatment against West Nile virus, which has been widely spread across the U.S., Canada, Latin America and the Caribbean.

"The goal of this latest research was twofold," said Chen. "First, we wanted to show proof-of-concept, demonstrating that tobacco plants can be used to manufacture large and complex MAb-based therapeutics. Second, we've wanted to improve the delivery of the therapeutic into the brain to combat West Nile virus at the place where it does the greatest harm."

More...

Researchers develop potentially safer and more cost-effective therapeutics against West Nile virus

Nasal spray delivers new type of depression treatment -- ScienceDaily

Nasal spray delivers new type of depression treatment

New drug multiplies analgesic effect of opioids without increasing constipation

Systemic (subcutaneous) or local (intraplantar) treatment of wild-type mice with the selective σ₁ antagonists BD-1063 [1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine dihydrochloride] or S1RA [4-[2-[[5-methyl-1-(2-naphthalenyl)1H-pyrazol-3-yl]oxy]ethyl] morpholine hydrochloride] potentiated μ-opioid antinociception; these effects were fully reversed by the σ₁agonist PRE-084 [2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate) hydrochloride], showing the selectivity of the pharmacological approach. The μ-opioid antinociception potentiated by σ₁ inhibition (by σ₁-receptor knockout orσ₁-pharmacological antagonism) was more sensitive to the peripherally restricted opioid antagonist naloxone methiodide than opioid antinociception under normal conditions, indicating a key role for peripheral opioid receptors in the enhanced antinociception. Direct interaction between the opioid drugs and σ₁ receptor cannot account for our results, since the former lacked affinity for σ₁ receptors (labeled with [³H](+)-pentazocine). A peripheral role for σ₁ receptors was also supported by their higher density (Western blot results) in peripheral nervous tissue (dorsal root ganglia) than in several central areas involved in opioid antinociception (dorsal spinal cord, basolateral amygdala, periaqueductal gray, and rostroventral medulla). In contrast to its effects on nociception, σ₁-receptor inhibition did not alter fentanyl- or loperamide-induced constipation, a peripherally mediated nonanalgesic opioid effect. Therefore, σ₁-receptor inhibition may be used as a systemic or local adjuvant to enhance peripheral μ-opioid analgesia without affecting opioid-induced constipation.

Ref : http://jpet.aspetjournals.org/content/348/1/32.abstract?sid=60aaa64d-fb66-459c-aded-4e971ab39aac


New drug multiplies analgesic effect of opioids without increasing constipation

New research raises hopes of new class of drugs to combat antibiotic resistant infections

New research raises hopes of new class of drugs to combat antibiotic resistant infections

Rotaxanes make symmetry history | Chemistry World

A UK team has stumbled upon an efficient way to separately produce each member of an unusual mirror image pair of chemical systemsthat has eluded scientists for over four decades.1Stephen Goldup and Robert Bordoli at Queen Mary University of London have made planar mechanically chiral rotaxanes, which trap macrocyclic rings along the shaft of dumbbell molecules. Goldup now wants to apply these newly accessible asymmetric assemblies in catalysis, sensing and materials. ‘We think it’s time that the advantages of mechanical chirality are properly investigated and begin to play a role,’ he tells Chemistry World....

Rotaxanes make symmetry history | Chemistry World

Caffeine-based compound with small amount of gold could be used as anticancer agent

The side effects of ingesting too much caffeine - restlessness, increased heart rate, having trouble sleeping - are well known, but recent research has shown that the stimulant also has a good side. It can kill cancer cells. Now, researchers report in the ACS journal Inorganic Chemistry that combining a caffeine-based compound with a small amount of gold could someday be used as an anticancer agent.

Angela Casini, Michel Picquet and colleagues note that caffeine and certain caffeine-based compounds have recently been in the spotlight as possible anticancer treatments. But drinking gallons of coffee, sodas and energy drinks isn't the solution. And the regular caffeine in these drinks would start to have negative effects on healthy cells, too, at the levels necessary to kill cancerous ones. Gold also can wipe out cancer cells, but, like caffeine, it can harm healthy cells. So, the research team put the two together into certain configurations to see whether the new caffeine-based gold compounds could selectively stop cancer cells from growing without hurting other cells.

They made a series of seven new compounds, called caffeine-based gold (I) N-heterocyclic carbenes, in the laboratory and studied them. The scientists found that, at certain concentrations, one of the compounds of the series selectively killed human ovarian cancer cells without harming healthy cells. In addition, the compound targeted a type of DNA architecture, called "G-quadruplex," that is associated with cancer.

Ref : http://pubs.acs.org/doi/abs/10.1021/ic403011h?prevSearch=Angela%2BCasini&searchHistoryKey=

Caffeine-based compound with small amount of gold could be used as anticancer agent

Triphase's marizomib receives FDA orphan drug designation for treatment of multiple myeloma

Salinosporamide A (Marizomib) is a potent proteasome inhibitor used as an anticancer agent that recently entered phase I human clinical trials for the treatment of multiple myeloma only three years after its discovery. This novel marine natural product is produced by the recently described obligate marine bacteria Salinispora tropica and Salinispora arenicola, which are found in ocean sediment. Salinosporamide A belongs to a family of compounds, known collectively as salinosporamides, which possess a densely functionalized γ-lactam-β-lactone bicyclic core.

Triphase Accelerator Corporation recentlyannounced that marizomib, its novel, potent proteasome inhibitor, has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA)'s Office of Orphan Products Development for the treatment of multiple myeloma. The orphan drug designation will provide Triphase with 7-year marketing exclusivity for marizomib and other benefits upon FDA approval.

"We are pleased that the FDA has granted orphan drug designation for the development of marizomib to benefit patients with multiple myeloma," said Frank Stonebanks, founder, president and CEO of Triphase. "While patients with refractory multiple myeloma are living longer and better lives as a result of medical innovation, there is still a need for new treatment options. We are excited to move forward with the development of marizomib, a potential best-in-class agent, and hope to advance the treatment paradigm that will turn this once acute disease into a long-term manageable disease."

Triphase's marizomib receives FDA orphan drug designation for treatment of multiple myeloma

Astellas Pharma to exclusively commercialize isavuconazole in the U.S. and Canada

Isavuconazole (BAL4815) is a triazole antifungal. Its prodrug, isavuconazonium sulfate (BAL8557) is currently in two Phase IIIclinical trials (SECURE and VITAL), the results of which are expected in the second half of 2013.

On May 28, 2013, Basilea Pharmaceutica, the maker of the drug, announced it had been granted orphan drug status by the U.S. Food and Drug Administration (FDA).

Now Astellas Pharma Inc. (Tokyo:4503, "Astellas") announced today that the company has amended the License, Co-Development and Co-Promotion Agreement on isavuconazole under co-development with Basilea Pharmaceutica Ltd. ("Basilea"). Based on this amendment, the territories subject to the License Agreement have been changed to reflect that Astellas will be responsible for all regulatory filings and will exclusively commercialize and assume full responsibility for manufacturing isavuconazole in the U.S. and Canada.

Astellas Pharma to exclusively commercialize isavuconazole in the U.S. and Canada

Researchers discover novel treatments for psoriasis that are likely to cause fewer side effects

In the article in Science Translational Medicine, which features Juan Guinea-Viniegra as the lead author, the authors state that: "blocking miR-21 could offer advantages over current treatments given that the efficiency obtained is the same and the side effects are probably reduced". The authors highlight that in the mouse model and in patient samples transplanted into mice this new strategy "shows a significant therapeutic response".

Researchers discover novel treatments for psoriasis that are likely to cause fewer side effects