A common, tiny tropical fish plays a key role in a new model for Cushing disease, giving researchers a powerful tool to conduct extensive searches for effective treatments for this serious hormonal disorder, testing up to 300 drugs weekly.
The model – published online on May 2 by the Proceedings of the National Academy of Sciences -- was created in the laboratory of Shlomo Melmed, MD, dean of the medical faculty at Cedars-Sinai, by his research team led by Ning-Ai Liu, MD, PhD.
They introduced into striped zebrafish – the freshwater translucent tropical Danio rario -- the “pituitary tumor transforming gene” discovered in Melmed’s lab in 1997. This caused the zebrafish to develop features of Cushing disease including: high levels of the stress-related hormone cortisol; diabetes; and heart disease. These zebrafish then were bred with fish that bear green fluorescent markers, allowing researchers to visualize in the resulting hybrids how drugs interact with the Cushing’s disease pituitary tumors.
“This new model for Cushing disease means that we can more rapidly and effectively identify drugs that could be successful in fighting these tumors,” Melmed said. “With no current drug therapies and limited options available to Cushing patients, it is our hope that our research will enable medical advances that will revolutionize how this disease is treated.”
Cushing Disease often is caused by a pituitary tumor that triggers overproduction of a hormone, which, in turn, stimulates the adrenal gland to overproduce cortisol, affecting nearly every area of the body including the regulation of blood pressure and metabolism. This leads to serious health problems, including diabetes, hypertension, osteoporosis, obesity (especially with a distinctive moon face and fatty tissue deposits in the midsection, upper back and between the shoulders) and cardiovascular disease.
There are no approved drugs that effectively target the pituitary tumors that frequently cause the disease. “Because the tumors can be too small to be detected by MRI and a complete tumor resection by surgery can be difficult in some cases, this leaves few treatment options for many with the disease,” said Dr. Liu, an endocrinologist at Cedars Sinai.
In the initial test of the zebrafish model, researchers studied five drugs, including R-roscovitine, a drug in phase two trials to treat esophageal and non-small cell lung cancer. This drug was found to effectively suppress levels of hormone secreted by the pituitary tumor, as well as the level of cortisol and could be a potential treatment for fighting tumor growth.
The study was supported by a National Institutes of Health Grant and the Doris Factor Molecular Endocrinology Laboratory.
Nicole White | Cedars-Sinai Medical Center
The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
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