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 Mental Disorders and Physical Diseases Co-occur in Teenagers
08.04.2015 | Universität Basel

nachricht Researchers observe major hand hygiene problems in operating rooms
30.03.2015 | University of Gothenburg

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: Advances in Molecular Electronics: Lights On – Molecule On

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and the University of Konstanz are working on storing and processing information on the level of single molecules to create the smallest possible components that will combine autonomously to form a circuit. As recently reported in the academic journal Advanced Science, the researchers can switch on the current flow through a single molecule for the first time with the help of light.

Dr. Artur Erbe, physicist at the HZDR, is convinced that in the future molecular electronics will open the door for novel and increasingly smaller – while also...

Im Focus: Pruning of Blood Vessels: Cells Can Fuse With Themselves

Cells of the vascular system of vertebrates can fuse with themselves. This process, which occurs when a blood vessel is no longer necessary and pruned, has now been described on the cellular level by Prof. Markus Affolter from the Biozentrum of the University of Basel. The findings of this study have been published in the journal “PLoS Biology”.

The vascular system is the supply network of the human organism and delivers oxygen and nutrients to the last corners of the body. So far, research on the...

Im Focus: Astronomers reveal supermassive black hole's intense magnetic field

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a supermassive black hole in a distant galaxy

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a...

Im Focus: A “pin ball machine” for atoms and photons

A team of physicists from MPQ, Caltech, and ICFO proposes the combination of nano-photonics with ultracold atoms for simulating quantum many-body systems and creating new states of matter.

Ultracold atoms in the so-called optical lattices, that are generated by crosswise superposition of laser beams, have been proven to be one of the most...

Im Focus: UV light robot to clean hospital rooms could help stop spread of 'superbugs'

Can a robot clean a hospital room just as well as a person?

According to new research out of the Texas A&M Health Science Center College of Medicine, that is indeed the case. Chetan Jinadatha, M.D., M.P.H., assistant...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

World Conference On Regenerative Medicine 2015: Registration And Abstract Submission Now Open

25.03.2015 | Event News

University presidents from all over the world meet in Hamburg

19.03.2015 | Event News

 
Latest News

High-Power Laser Spinoff Proves Versatility Is Strength

20.04.2015 | Physics and Astronomy

New “Cool Roof Time Machine” Will Accelerate Cool Roof Deployment

20.04.2015 | Architecture and Construction

STAR Heavy Flavor Tracker Detects Signs of Charm at RHIC

20.04.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>