Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study suggests repurposing anti-depressant medication to target medulloblastoma

25.08.2014

An international research team reports in Nature Medicine a novel molecular pathway that causes an aggressive form of medulloblastoma, and suggests repurposing an anti-depressant medication to target the new pathway may help combat one of the most common brain cancers in children.

The multi-institutional group, led by scientists at Cancer and Blood Diseases Institute (CBDI) at Cincinnati Children's Hospital Medical Center, publish their results in the journal's online edition on Aug. 24. The researchers suggest their laboratory findings in mouse models of the disease could lead to a more targeted and effective molecular therapy that would also reduce the harmful side effects of current treatments, which include chemotherapy, radiation or surgery.

"Although current treatments improve survival rates, patients suffer severe side effects and relapse tumors carry mutations that resist treatment," said lead investigator Q. Richard Lu, PhD, scientific director of the Brain Tumor Center, part of the CBDI at Cincinnati Children's. "This underscores an urgent need for alternative targeted therapies, and we have identified a potent tumor suppressor that could help a subset of patients with an aggressive form of medulloblastoma."

Using genetically-engineered mice to model human medulloblastoma, the authors identified a gene called GNAS that encodes a protein called Gsa. Gsa kicks off a signaling cascade that researchers found suppresses the initiation of an aggressive form of medulloblastoma driven by a protein called Sonic hedgehog – considered one of the most important molecules in tissue formation and development.

The scientists used an anti-depressant medication called Rolipram – approved for behavioral therapy for use in Europe and Japan – to treat mice that were engineered not to express the GNAS gene. Lack of GNAS allowed aggressive formation of medulloblastoma tumors in neural progenitor cells of the GNAS mutant mice.

Rolipram treatment in the mice elevated levels of a molecule called cAMP, which restored the GNAS-Gsa pathway's tumor suppression function. This caused the tumors to shrink and subside. The study also suggests that elevating cAMP levels in cells enhances the potency of Sonic hedgehog inhibitors, currently being tested in clinical trials to fight tumor growth.

The scientists stressed that a significant amount of additional research is needed before their findings could become directly relevant to clinical treatment. The authors also caution that the effect of raising cAMP levels may depend on the type of cancer, and that laboratory results in mice do not always translate uniformly to humans.

###

Collaborating on the study with Dr. Lu was first author, Xuelian He (MD, a postdoctoral fellow), of the CBDI at Cincinnati Children's and the West China Second Hospital, Sichuan University, in Chengdu, China.

Other collaborating institutions include: The Hospital for Sick Children, University of Toronto, Toronto; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea; the German Cancer Research Center, Heidelberg, Germany; the National Institute of Diabetes and Digestive and Kidney Diseases (NIH); Department of Neurology, Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston; St. Jude Children's Research Hospital, Memphis; departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine, St Louis; Tumor Development Program, Sanford-Burnham Medical Research Institute, La Jolla, Calif.

Funding support came in part from the National Institutes of Health (R01NS078092, R01NS075243) and the Canadian Institutes of Health Research.

About Cincinnati Children's:

Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2014 Best Children's Hospitals. It is also ranked in the top 10 for all 10 pediatric specialties. Cincinnati Children's, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at http://www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.

Nick Miller | Eurek Alert!

More articles from Studies and Analyses:

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

nachricht Brain connectivity reveals hidden motives
04.03.2016 | Universität Zürich

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First experimental quantum simulation of particle physics phenomena

Physicists in Innsbruck have realized the first quantum simulation of lattice gauge theories, building a bridge between high-energy theory and atomic physics. In the journal Nature, Rainer Blatt‘s and Peter Zoller’s research teams describe how they simulated the creation of elementary particle pairs out of the vacuum by using a quantum computer.

Elementary particles are the fundamental buildings blocks of matter, and their properties are described by the Standard Model of particle physics. The...

Im Focus: Is There Life On Mars?

Survivalist back from Space - 18 months on the outer skin of the ISS

A year and a half on the outer wall of the International Space Station ISS in altitude of 400 kilometers is a real challenge. Whether a primordial bacterium...

Im Focus: CWRU physicists deploy magnetic vortex to control electron spin

Potential technology for quantum computing, keener sensors

Researchers at Case Western Reserve University have developed a way to swiftly and precisely control electron spins at room temperature.

Im Focus: Physicists measured something new in the radioactive decay of neutrons

The experiment inspired theorists; future ones could reveal new physics

A physics experiment performed at the National Institute of Standards and Technology (NIST) has enhanced scientists' understanding of how free neutrons decay...

Im Focus: Discovery of gold nanocluster 'double' hints at other shape changing particles

New analysis approach brings two unique atomic structures into focus

Chemically the same, graphite and diamonds are as physically distinct as two minerals can be, one opaque and soft, the other translucent and hard. What makes...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ERES 2016: The largest conference in the European real estate industry

09.06.2016 | Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

 
Latest News

Nanoscientists develop the 'ultimate discovery tool'

24.06.2016 | Materials Sciences

Russian physicists create a high-precision 'quantum ruler'

24.06.2016 | Physics and Astronomy

Hubble confirms new dark spot on Neptune

24.06.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>