Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover new way to kill pediatric brain tumors

10.02.2010
Researchers at Washington University School of Medicine in St. Louis have shown once again that "ready, fire, aim," nonsensical though it may sound, can be an essential approach to research.

The scientists robotically "fired" 2,000 compounds into culture plates containing tumor cells to see if the compounds had any effect. When the robotic screener found one substance had scored a hit by inhibiting growth of the tumor cells in its plate, researchers analyzed what that compound acted against. Follow-up studies showed that the drug slowed tumor growth in mice by inhibiting the function of a protein called STAT3.

As a result, researchers now have a previously unrecognized target, STAT3, at which they can "aim" new drugs for the treatment of cancer in neurofibromatosis-1 (NF1), a genetic condition that causes increased risk of benign and malignant brain tumors.

"We were excited to find that the slowed tumor growth we observed following treatment resulted from increased tumor cell death — an effect we hadn't seen before when we blocked other NF1 growth control molecules," says senior author David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology. "Now we can identify the genes that STAT3 influences to fine-tune our treatments and ensure that we kill cancer cells with minimal harm to normal cells."

Gutmann is director of the Neurofibromatosis Center at Washington University, a national referral center for patients with all forms of neurofibromatosis. The center is active both in clinical trials and in basic research to help develop innovative new approaches for treating patients with NF. Gutmann is also co-director of the neuro-oncology program at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

Gutmann collaborated on this project with David Piwnica-Worms, M.D., Ph.D., professor of radiology and of developmental biology and director of the Molecular Imaging Center at Washington University. The results appear this month in the journal Cancer Research.

Cucurbitacin-I, the compound that led scientists to STAT3, is a plant steroid. It belongs to a family of bitter-tasting compounds previously identified as inhibitors of STAT3. Gutmann says cucurbitacin-I is likely too toxic to be suitable for use in clinical trials at this time.

After the successful robotic test of cucurbitacin-I, researchers showed that STAT3, which turns on and off the activity of a number of genes, is unusually active in NF1 tumor cells. Further investigation revealed that STAT3 activity is regulated by another gene very familiar to Gutmann: the mammalian target of rapamycin (mTOR).

Gutmann's laboratory linked mTOR and the processes it controls to NF1 years ago. The new connection between STAT3 and the mTOR pathway makes STAT3 the last link in a chain of molecules that take growth-promoting signals from the cell membrane to the nucleus. Gutmann says he is encouraged by the possibility that scientists might be able to decipher the genetic program controlled by STAT3 in order to develop more refined treatments for tumors in patients with NF1.

"We went in with a 'we don't know enough' approach, let's try 'ready, fire, aim,' and it paid off," he says.

Banerjee S, Byrd JN, Gianino SM, Harpstrite SE, Rodriguez FJ, Tuskan RG, Reilly KM, Piwnica-Worms DR, Gutmann DH. Neurofibromin controls cell growth by regulating signal transducer and activator of transcription 3 activity in vitro and in vivo. Cancer Research, Feb. 15, 2010.

Funding from the Department of Defense, the National Institutes of Health and the Siteman Cancer Center supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht New type of photosynthesis discovered
17.06.2018 | Imperial College London

nachricht New ID pictures of conducting polymers discover a surprise ABBA fan
17.06.2018 | University of Warwick

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

Im Focus: Water is not the same as water

Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.

From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

A sprinkle of platinum nanoparticles onto graphene makes brain probes more sensitive

15.06.2018 | Materials Sciences

100 % Organic Farming in Bhutan – a Realistic Target?

15.06.2018 | Ecology, The Environment and Conservation

Perovskite-silicon solar cell research collaboration hits 25.2% efficiency

15.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>