Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pediatric brain tumors

21.09.2011
Regulatory protein represents potential drug target

Medulloblastomas constitute the most frequent class of malignant childhood brain tumor. Tumors of this type arise due to the uncontrolled proliferation of immature nerve cells in the developing brain, and there is no targeted treatment available.

A research team based at LMU‘s Center for Neuropathology and Prion Research and led by Privatdozent Dr. Ulrich Schüller has now demonstrated that the regulatory protein FoxM1 is essential for the continued growth of these tumor cells. Moreover, the level of FoxM1 expressed in the cells is significantly, and negatively, correlated with a patient’s survival time.

The protein therefore provides a useful prognostic marker, which should allow oncologists to gauge the malignancy of tumors and select the most effective therapeutic strategy for the individual patient. Furthermore, FoxM1 may provide a novel point of attack for the development of new ways to treat the condition. Schüller and his team were able to reduce FoxM1 levels in tumor cells by exposing them to the antibiotic siomycin A, and showed that the drug also inhibits tumor growth. “If further work on laboratory cell cultures and in living organisms confirms these results, siomycin could turn out to be an effective drug for the treatment of medulloblastoma,” Schüller says. (Clinical Cancer Research, published OnlineFirst 14.September 2011)

Research conducted over the past 10 years has shown that medulloblastomas arise as a result of aberrant activation of certain molecular signaling pathways. Schüller and his team set out to determine whether the transcription factor FoxM1 plays a role in supporting the growth of this type of tumor and, if so, whether it might serve as a drug target for the development of an effective therapy for the disease.

Transcription factors determine the suite of proteins present in a given cell by defining which of the genes encoded in the genomic DNA are transcribed into RNA copies that can program protein synthesis. The so-called Forkhead-box (Fox) proteins are transcription factors that are particularly concerned with the regulation of cell growth, division and differentiation, and fully differentiated cells do not proliferate further. FoxM1 activates genes that promote cell division and simultaneously turns off genes that inhibit proliferation. Since uncontrolled proliferation is the basic hallmark of cancer cells, understanding and manipulating the function of FoxM1 has become a focus of cancer research. In several different types of cancer, including cancers of the breast, lung and prostate gland, increased amounts of FoxM1 have been found in tumor tissue. Indeed the protein has been shown to be necessary for growth of these tumors. Schüller and his team have now shown that this also true for medulloblastomas.

“One important result was that the amount of FoxM1 present in medulloblastoma cells is correlated with patient survival time,” says Schüller. Since it is relatively easy to estimate FoxM1 levels using laboratory tests, the molecule could possibly be used as a prognostic marker to guide the choice of treatment for each patient. Modern therapeutic options for medulloblastoma involve surgical removal of the tumor, followed by radiation and chemotherapy to eliminate any surviving tumor cells, but this approach is associated with serious side-effects. Furthermore, there are six different subtypes of medulloblastoma, which differ markedly in their malignancy and clinical prognosis. “That is why a good prognostic marker with which one could predict the aggressivity of tumors would be so useful,” says Schüller. The clinician could then adapt the therapeutic approach to the patient’s individual needs, and thus avoid using a sledgehammer to crack a nut.

Since FoxM1 is indispensable for the growth of medulloblastoma cells, it represents a potentially ideal drug target. With the aid of the antibiotic siomycin A, which specifically inhibits the production of FoxM1, Schüller was indeed able to inhibit the growth of medulloblastoma cells. These findings confirm and extend results obtained by other groups who have reported that siomycin A also hinders the growth of breast cancer cells. – And most importantly, Schüller‘s experiments showed that although FoxM1 is essential for tumor growth, other factors can apparently substitute for it during normal development. Hence blocking the action of FoxM1 by administering siomycin A should have no untoward effects on normal cells. Thus the antibiotic may make it possible, for the first time, to intervene directly and specifically in the process that gives rise to medulloblastomas, and provide the first therapeutic option that targets a major driver of the growth of such tumors.

The work was carried out by the Max Eder Junior Research Group in Pediatric Neuro-oncology, which is led by Ulrich Schüller and is supported by grants from the Deutsche Krebshilfe. (göd/PH)

Publication:
Expression of FoxM1 is required for the proliferation of medulloblastoma cells and indicates worse survival of patients.
M. Priller, J. Pöschl, L. Abrao, A.O. von Bueren, Y.-J. Cho, S. Rutkowski, H.A. Kretzschmar, U. Schüller
Clinical Cancer Research, Published OnlineFirst 14. September 2011
doi: 10.1158/1078-0432.CCR-11-1214
Contact:
Priv.-Doz. Dr. med. Ulrich Schüller
Center for Neuropathology
LMU Munich
Phone: +49 89 2180 78114
Fax: +49 89 2180 78037
Email: ulrich.schueller@med.uni-muenchen.de

Dr. Kathrin Bilgeri | EurekAlert!
Further information:
http://www.neuropathologie.med.uni-muenchen.de

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>