"We are excited about this finding because there are so few treatment options for pulmonary hypertension," said study author Mardi Gomberg-Maitland, M.D., M.Sc., assistant professor of medicine at the University of Chicago. "We have drugs that can slow progression of the disease but nothing that can stop or reverse the process. This is a ray of hope."
Pulmonary hypertension and cancer share certain features. Both diseases involve abnormal cellular growth. These abnormal cells – in the case of pulmonary hypertension, those that line the blood vessels leading to the lungs – release signals that stimulate the growth of small new blood vessels to feed the renegade cells, allowing further proliferation, and thickening of the vessel walls. Sorafenib appears to interfere with that process.
Although originally designed to fight colon cancer, the drug, sorafenib (Nexavar®), proved much more effective against kidney cancer. Sorafenib inhibits an enzyme, known as Raf kinase, which plays a role in tumor-cell growth. Researchers eventually realized it also hit other targets. After clinical trials in kidney cancer patients demonstrated improved survival, it won FDA approval in December 2005.
Now, in a surprise finding, it appears to have a use in treating this cardiovascular disease.
In pulmonary hypertension, the vessels that carry blood from the heart to the lungs constrict. Their walls thicken, which narrows the opening and reduces blood flow. Pressures within the arteries build up, requiring the heart to pump harder to push blood through the narrowed tubes to the lungs. Eventually the heart can no longer keep up. Less and less blood reaches the lungs, the heart enlarges to try to overcome the pressure, and damage to the overworked heart accumulates.
Although treatment for pulmonary hypertension has improved, long-term survival, even with therapy, is disappointing, similar to that for lung cancer. Because sorafenib inhibits the chemical signals that can trigger both cellular proliferation and new blood vessel growth, Gomberg-Maitland and colleagues suspected it might slow the growth and thickening of the pulmonary artery walls.
To test this theory they treated rats at high risk for pulmonary hypertension with sorafenib. The researchers studied five groups of rats. One group stayed in normal cages and received no medication. The other four groups spent three weeks in a low-oxygen environment – about half the normal level – which can trigger pulmonary hypertension. Rats in the reduced-oxygen chambers received: no medication, a drug called SU5416 (well known to cause severe pulmonary hypertension in this setting), SU5416 plus sorafenib, or sorafenib alone.
As expected, the unmedicated rats in a low-oxygen environment had mildly elevated pulmonary artery pressures after three weeks and those that received SU5416 developed severe pulmonary hypertension. But, those that received sorafenib or sorafenib plus S5416, had negligible pressure increases. Sorafenib appeared not only to counteract the effects of the low-oxygen environment but also to prevent the additional damage caused by SU5416.
"This was an encouraging sign," said Gomberg-Maitland. This is "one of the best models we have for this disease," she said.
The side effects of the drug in humans have been relatively mild. The most common adverse effects are: rashes of the face and arms or hands and feet, mild diarrhea, and fatigue.
A phase-1 clinical trial of the drug in human patients with pulmonary hypertension is expected to begin this winter.
John Easton | EurekAlert!
NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University
How to turn white fat brown
07.12.2016 | University of Pennsylvania School of Medicine
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine