Monday, February 18, 2013

Study describes pharmacological action of TZDs directly on pancreas

Study describes pharmacological action of TZDs directly on pancreas

Copper can protect against Alzheimer's disease

Copper can protect against Alzheimer's disease

Breakthrough in ovarian cancer: Selumetinib

In continuation  of my update on Seumetinab


We know that, Selumetinib (AZD6244) is a drug being investigated for the treatment of various types of cancer, for example non-small cell lung cancer (NSCLC). 
Mode of action : The gene BRAF is part of the MAPK/ERK pathway, a chain of proteins in cells that communicates input from growth factors. Activating mutations in the BRAF gene, primarily V600E (meaning that the amino acid valine in position 600 is replaced by glutamic acid), are associated with lower survival rates in patients with papillary thyroid cancer. Another type of mutation that leads to undue activation of this pathway occurs in the gene KRAS and is found in NSCLC. A possibility of reducing the activity of the MAPK/ERK pathway is to block the enzyme MAPK kinase (MEK), immediately downstream of BRAF, with the drug selumetinib. More specifically, selumetinib blocks the subtypes MEK1 and MEK2 of this enzyme....



The study was initially developed in 2007, with 52 patients enrolled for the Phase II clinical trial between December 2007 and November 2009. Patients were given 50 milligrams of selumetinib orally twice daily. Of those participants, eight had a measurable decrease in tumor size, seven had partial responses and 34 patients saw their tumors stabilize. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in patients with low-grade ovarian cancer.

"There just aren't very good treatments for low-grade ovarian cancer, so this discovery opens up a lot of new exciting possibilities for us," Dr. Farley said. He added that Phase III of this trial is scheduled to begin in the next few weeks, with that trial to be the "definitive test" before the treatment becomes available to the general population.


Ref : http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70572-7/fulltext



Breakthrough in ovarian cancer: Selumetinib

Saturday, February 16, 2013

Nitric oxide: A little molecule's remarkable feat -- prolonging life, worm study shows

FDA Approves Pomalyst for Advanced Multiple Myeloma

We know that, Pomalidomide (INN, originally CC-4047 or 3-amino-thalidomide, marketed as Pomalyst by Celgene), is a derivative of thalidomide that is anti-angiogenic and also acts as an immunomodulator. Pomalidomide was approved on February 8, 2013 by the U.S. Food and Drug Administration (FDA) as a treatment for relapsed and refractory multiple myeloma....



Friday, February 15, 2013

FDA Approves Ravicti for the Chronic Management of Some Urea Cycle Disorders

The U.S. Food and Drug Administration today approved Ravicti (glycerol phenylbutyrate) for the chronic management of some urea cycle disorders (UCDs) in patients ages 2 years and older.

UCDs are genetic disorders that involve deficiencies of specific enzymes involved in the urea cycle, a series of biochemical steps normally required to remove ammonia from the blood. When protein is absorbed and broken down by the body, it produces nitrogen as a waste product. The urea cycle removes nitrogen from the blood and converts it to urea, which is removed from the body through urine. In people with UCDs, nitrogen accumulates and remains in the body as ammonia, which can travel to the brain and cause brain damage, coma or death.


Wednesday, February 13, 2013

'Clot-Buster' Drug May Still Be Best Stroke Treatment - Drugs.com MedNews

Top-line results from Vanda's tasimelteon Phase IIb/III study on major depressive disorder

We know that, Tasimelteon (BMS-214,778) is a drug which is under development for the treatment of insomnia and other sleep disorders. It is a selective agonist for the melatonin receptors MT1 and MT2 in the suprachiasmatic nucleus of the brain, similar to older drugs such as ramelteon. It has been through Phase III trials successfully and was shown to improve both onset and maintenance of sleep, with few side effects.

A year-long (2011-2012) study at Harvard is testing the use of tasimelteon in blind subjects with non-24-hour sleep-wake disorder.
Now Vanda Pharmaceuticals Inc. (NASDAQ: VNDA),  announced top-line results of the Phase IIb/III clinical study (MAGELLAN) in Major Depressive Disorder (MDD), investigating the efficacy and safety of tasimelteon as a monotherapy in the treatment of patients with MDD.  The clinical study did not meet the primary endpoint of change from baseline in the Hamilton Depression Scale (HAMD-17) after 8 weeks of treatment as compared to placebo.  Both tasimelteon and placebo treated patients had an approximately 40% reduction of their MDD symptoms from baseline.  Tasimelteon was shown to be safe and well-tolerated, consistent with observations in prior studies.  Given these current proof of concept clinical study results, Vanda has decided to discontinue all activities in this indication.

"These results are disappointing, as there is still a significant unmet medical need for patients with Major Depression," said Mihael H. Polymeropoulos , M.D., President and CEO of Vanda.  "Tasimelteon's application in the treatment of blind individuals with Non-24 remains our top priority as we pursue our planned NDA submission this year."     

Vanda has recently reported positive results in two phase III clinical studies of tasimelteon in Non-24-Hour Disorder (Non-24) and plans to submit a New Drug Application to the U.S. Food and Drug Administration in mid-2013......

Tuesday, February 12, 2013

Hops, Key to Flavor in Beer, May Prove Useful in New Drugs - Drugs.com MedNews

We know that, Humulone (α-lupulic acid) is a bitter-tasting chemical compound found in the resin of mature hops (Humulus lupulus). Humulone is a prevalent member of the class of compounds known as alpha acids, which collectively give beer its characteristic bitter flavor.

In a  new study, researchers determined the precise configuration of humulones, substances derived from hops that give beer its unique flavor.

"Now that we have the right results, what happens to the bitter hops in the beer-brewing process makes a lot more sense," study lead author Werner Kaminsky, a University of Washingto.

Previous research has suggested that moderate consumption of beer  and therefore its bitter compounds might have positive effects on diseases such as diabetes and some types of cancer, as well as aiding weight loss and decreasing inflammation. 

The new findings could help scientists determine which humulones might prove useful in efforts to develop new drugs, Kaminsky said.

The authors wrote in their report that while "excessive beer consumption cannot be recommended to propagate good health  isolated humulones and their derivatives can be prescribed with documented health benefits."

Ref : http://onlinelibrary.wiley.com/doi/10.1002/anie.201208450/abstract
  

Sunday, February 10, 2013

Messenger RNA–Based Vaccines for Cancer | Articles | Drug Discovery and Development Magazine

Nucleic acids are being extensively investigated for use in gene therapy and in genetic vaccinations in which foreign nucleic acid is translated into proteins by the host cells. Vaccines based on DNA and messenger RNA (mRNA) are able to stimulate all effectors of the adaptive immune response: B lymphocytes, cytotoxic T cells, and T helper cells. This makes them a useful tool in the creation of prophylactic vaccines for infectious diseases and for cancer immunotherapy.

Saturday, February 9, 2013

Phenformin decreases size of lung tumors and increases survival in mice

In continuation of my update on metformin and phenformin
In a new study in the journal Cancer Cell, Shaw and a team of scientists at the Salk Institute for Biological Studies found that phenformin, a derivative of the widely-used diabetes drug metformin, decreased the size of lung tumors in mice and increased the animals' survival. The findings may give hope to the nearly 30 percent of patients with non-small cell lung cancer (NSCLC) whose tumors lack LKB1 (also called STK11).

The LKB1 gene turns on a metabolic enzyme called AMPK when energy levels of ATP, molecules that store the energy we need for just about everything we do, run low in cells. In a previous study, Shaw, an associate professor in Salk's Molecular and Cell Biology Laboratory and researcher in the Institute's new Helmsley Center for Genomic Medicine, demonstrated that cells lacking a normal copy of the LKB1 gene fail to activate AMPK in response to low energy levels. LKB1-dependent activation of AMPK serves as a low-energy checkpoint in the cell. Cells that lack LKB1 are unable to sense such metabolic stress and initiate the process to restore their ATP levels following a metabolic change. As a result, these LKB1-mutant cells run out of cellular energy and undergo apoptosis, or programmed cell death, whereas cells with intact LKB1 are alerted to the crisis and re-correct their metabolism.


"The driving idea behind the research is knowing that AMPK serves as a sensor for low energy loss in cells and that LKB1-deficient cells lack the ability to activate AMPK and sense energy loss," says David Shackelford, a postdoctoral researcher at Salk who spearheaded the study in Shaw's lab and is now an assistant professor at UCLA's David Geffen School of Medicine.


That led Shaw and his team to a class of drugs called biguanides, which lower cellular energy levels by attacking the power stations of the cell, called mitochondria. Metformin and phenformin both inhibit mitochondria; however, phenformin is nearly 50 times as potent as metformin. In the study, the researchers tested phenformin as a chemotherapy agent in genetically-engineered mice lacking LKB1 and which had advanced stage lung tumors. After three weeks of treatment, Shaw and his team saw a modest reduction in tumor burden in the mice.

Ref : https://www.cell.com/cancer-cell/abstract/S1535-6108%2812%2900518-1

Friday, February 8, 2013

Can Brightly Colored Fruits, Veggies Protect Against ALS? - Drugs.com MedNews

Researchers from Harvard School of Public Health have,  found that increasing consumption of carotenoids, particularly beta-carotene and lutein, might reduce the risk for this progressive neurological disease, which attacks nerve cells in the brain and spinal cord.


Carrots, yams and mangoes are rich in beta-carotenes, and spinach, collard greens and egg yolks are good sources of lutein. The study found, however, that diets rich in the antioxidants lycopene, beta-cryptoxanthin and vitamin C do not apparently reduce the risk for ALS, which causes the muscles to waste away and eventually results in paralysis.

"ALS is a devastating degenerative disease that generally develops between the ages of 40 and 70, and affects more men than women," senior study author Dr. Alberto Ascherio, a professor of epidemiology and nutrition at Harvard School of Public Health, said in a journal news release. "Understanding the impact of food consumption on ALS development is important."

Analyzing information on more than 1 million people, the researchers identified nearly 1,100 cases of ALS. The researchers found that increased overall carotenoid intake -- especially among those who ate diets rich in beta-carotene and lutein -- seemed to be linked to a lower risk for the devastating condition. 


Those who ate more carotenoids daily also were more likely to exercise, have an advanced degree, have increased vitamin C intake and take vitamin C and E supplements.

The researchers pointed out, however, that long-term vitamin C supplements did not lower people's risk for this degenerative disease.


"Our findings suggest that consuming carotenoid-rich foods may help prevent or delay the onset of ALS," Ascherio concluded. "Further food-based analyses are needed to examine the impact of dietary nutrients on ALS."

 Ref : http://onlinelibrary.wiley.com/doi/10.1002/ana.23820/abstract