FDA has approved two drugs to GlaxoSmithKline for the treatment of advanced melanoma - the most aggressive skin cancer patients with specific genetic mutations. Regulatory approvals, and diagnostic test for demonstrating these mutations.
 
The drugs are approved for administration separately, once in two separate clinical trials, they showed delayed tumor growth.

After decades of virtually no progress in the fight against advanced melanoma, two new drugs celebrated turn in favor of medicine. Over the past two years, FDA has approved a total of 4 new drugs this indication.
 
Each year in the U.S. from melanoma ill about 75 000 people. The mortality rate is around 9,000 to 10,000 per year.
 
Forecast sales for each of the two new drugs are about 350 million dollars a year.

According to a study published in the journal The Lancet, confirmed the first cases of resistance in avian influenza virus strain N7N9 to Tamiflu and related drugs. The study, conducted by the team of Dr. Yang from the Shanghai Center for Public Health, has been described as one of the finest virology research done so far.

The team examined 14 people infected with the strain N7N9, and track viral load (the content of virus in the blood) in the course of treatment. All study participants developed pneumonia. Seven of them require assisted ventilation, and three others - from extracorporeal membrane oxygenation of the blood - a procedure in which blood is oxygenated using an external device, as the lungs do not function properly. Two of these patients die after the infection.

Researchers found that 11 patients Tamiflu lowers viral load, while most seriously ill he continued to grow, even during treatment. According to the team, this means that the strain acquired resistance to Tamiflu, and maybe even the entire class of drugs called neuraminidase inhibitors.

Assumption was later confirmed by genetic studies of viruses that detect mutations characteristic of neuraminidase inhibitor-resistant strains. This is the first study linking these mutations with resistance in strains N7N9. According to the authors, in all cases, early treatment provides the best chance of recovery.
 
Earlier this month, reports surfaced that N7N9 strain can spread from person to person. According to the World Health Organization is currently developing a vaccine that provides immunity against the agent.

In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe cases of the disease, the immune system makes a unique subset of antibodies that have a disease-promoting role.

Reporting in the journal Science Translational Medicine online May 22, the Johns Hopkins team describes how it found the novel antibodies to peptidylarginine deiminase 4, or PAD4, in blood samples from people with aggressive inflammation and connective tissue damage.

Researchers say the presence of so-called PAD3/PAD4 cross-reactive autoantibodies could serve as the basis for the first antibody-specific diagnostic test to distinguish those with severe rheumatoid arthritis from those with less aggressive forms of the disease.
"Identifying early on a subset of patients with severe rheumatoid arthritis could benefit their health, as these patients could start aggressive drug therapy immediately and find the most effective treatment option," says senior study investigator Antony Rosen, M.D. Rosen, director of rheumatology and the Mary Betty Stevens Professor at the Johns Hopkins University School of Medicine, says that a third, or 1 million of the more than 3 million Americans -- mostly women -- estimated to have rheumatoid arthritis have an aggressive form of the disease.
In the study, the antibodies were present -- in 18 percent of 44 fluid samples from one research collection and in 12 percent of another collection of 194 -- but only in people with severe cases of rheumatoid arthritis. Past research shows that those with the most aggressive disease are less likely to respond to anti-inflammatory treatments with steroids and other drugs.
An examination of patients' medical records revealed that 80 percent of patients with the antibody saw their disease worsen over the previous year, while only 53 percent without the antibody showed disease progression. In comparing average scores of disease-damaged joints, researchers found that those with the antibody had an average deterioration in joints and bones by a score of 49. Those without the antibody had an average degradation in their score of 7.5, indicating much milder disease.
In a related finding, the Johns Hopkins team also uncovered how the PAD3/PAD4 cross-reactive auto-antibodies might contribute to more severe, erosive disease in rheumatoid arthritis. The team performed a series of experiments to gauge the antibodies' effects on PAD4 in response to varying cell levels of calcium, on which PAD enzymes depend.
Lab experiments showed that the antibodies greatly increase PAD4 enzyme function at the low levels of calcium normally present in human cells. Results showed that PAD4 activity was 500 times greater in the presence of antibodies than when they were absent. Tests of the antibody and enzymes' chemical structures later showed that the antibodies bind to PAD4 in the same region as calcium, suggesting to researchers that the antibodies might be substituting for calcium in activating the enzyme.
According to Rosen, the series of experiments, which took two years to complete, represents the first evidence of an antibody having a direct role in generating the targets of the immune response, or auto-antigens, in rheumatoid arthritis.
"Our results suggest that drugs inhibiting the PAD4 enzyme may have real benefit in patients with severe rheumatoid arthritis and represent an important field of study for investigating new and alternative treatments," says lead study investigator and biologist Erika Darrah, Ph.D.
Darrah says the team next plans long-term monitoring of arthritis sufferers to find out when the antibody first appears in the blood, and when intervention may have maximum impact in preventing or stalling disease progression. The team also plans further experiments to see if the antibody is taking control of the chemical pathways normally used by other cell proteins to control PAD4 sensitivity to calcium.
Funding support for this study was provided by the National Institutes of Health, and corresponding grant number T32-AR048522; the American College of Rheumatology; the Donald B. and Dorothy L. Stabler Foundation; and Sibley Memorial Hospital.
In addition to Rosen and Darrah, other Johns Hopkins researchers involved in this study were Jon Giles, M.D.; Michelle Ols, Ph.D.; and Felipe Andrade, M.D., Ph.D. Additional research assistance was provided by enzymologist Herbert Bull, Ph.D.

In the ongoing battle between humans and cockroaches, the insects have a leg up. A new study finds that roaches evolved their taste buds to make sweet insecticide baits taste bitter. As a result, the roaches avoid the baits and thrive, to the frustration of homeowners everywhere.

Plenty of insects evolve resistance to pesticides; they gain the ability to break down poisons without dying. German cockroaches, on the other hand, evolved what's known as a behavioral resistance to baits. They simply stopped eating them.

"Our paper is the first to show the sensory mechanism that underlies that behavioral resistance," said study researcher Coby Schal, an entomologist at North Carolina State University.

The answer, Schal and his colleagues found, is in the taste buds.

Evolving cockroaches

German cockroaches are the small, scuttling roaches frequently seen in human habitats, including homes and restaurants. They grow to be about a half-inch (1.27 centimeters) long and are omnivorous, scavenging everything from grease to starch.

"They'll eat pretty much anything in the kitchen, but they are incredibly good at eating things that are adaptive to them," Schal told LiveScience. "They are really amazingly good at learning to associate smells with specific tastes."

Beginning in the 1980s, many pest control companies switched from using spray insecticides to control cockroaches to using baits. The baits combine sugars with insecticide so that roaches eat them, thinking they are sugary snacks, return to their nests and die. Ideally, the other cockroaches in the nest then cannibalize their dead relative, getting a dose of the poison, too.

This worked beautifully — for a while. But in 1993, NC State entomologist Jules Silverman noticed that several populations of German cockroaches around the world were thriving in spite of the baits. The roaches were refusing to eat the glucose, or sugar, that was supposed to make the bait appealing.

Bitter or sweet?

Pest control companies switched up the sugars in their baits to keep them working, and for years, no one knew how the roaches had developed their glucose aversion. Now, Schal, Silverman and NC State postdoctoral researcher Ayako Wada-Katsumata have the answer.

The first question, Schal said, was whether there was a change in the brains or the sensory systems of the glucose-averse roaches. To find out, Wada-Katsumata conducted a delicate procedure in which she sedated roaches with ice, immobilized them and attached electrodes to the taste hairs on the cockroach mouthparts. These taste hairs act like taste buds on the human tongue, detecting chemical signals and sending them to the insect's central nervous system.

In normal roaches, some of the cells in the taste hairs respond to bitter tastes and others to sweet tastes. In roaches that avoided glucose, however, there was one change.

"The system was perfectly normal, except for the fact that glucose was being recognized not only by the sweet-responding cell, but also by the bitter-responding cell," Schal said.

In other words, the glucose-averse roaches tasted sweet things as bitter and thus avoided them. (Even cockroaches have standards, it seems.)

Roaches could have evolved this response simply because people started poisoning them with sweet baits, Schal said. It's also possible that the trait goes way back in cockroaches' 350-million-year history. Some plants produce toxic bittersweet compounds that roaches would have needed to avoid before humans came around. Once humans started building dwellings and roaches moved in, they may have lost this sugar-avoidance ability in order to snack on humans' leftovers. When people started developing sugary baits, the preadapted anti-sugar trait may have re-emerged, Schal said.

Either way, Schal said, the finding has implications for pest control. The industry has replaced glucose in baits with another sugar, fructose, but evidence already suggests that roaches are evolving to avoid fructose, too, he said. The industry needs to vary baits frequently and make multiple types at once to stay a step ahead of the roaches, he said.

"If you put out a little dab of bait and see that the cockroach bounces back from it, there's no point of using that bait," Schal said.