Navigation Links
Researchers discover new way to kill pediatric brain tumors
Date:2/9/2010

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.


'/>"/>
Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

Related medicine news :

1. UH Case Medical Center researchers publish promising findings for advanced cervical cancer
2. Researchers map all the fragile sites of the yeast Saccharomyces cerevisiaes genome
3. UCSF Researchers Identify Regulator of Human Sperm Cells
4. Researchers find broad spectrum antiviral that fights multitude of viruses
5. Caregivers of ICU patients are collateral damage of critical illness, say Pitt researchers
6. Researchers fight world hunger by mapping the soybean genome
7. HIV researchers solve key puzzle after 20 years of trying
8. UC Davis researchers identify brain protein for synapse development
9. UCLA cancer researchers perform complete genomic sequencing of brain cancer cell line
10. Researchers find new way to study how enzymes repair DNA damage
11. UCLA researchers image earliest signs of Alzheimers, before symptoms appear
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... Sterling, VA (PRWEB) , ... April 29, 2016 ... ... Americans with student loans more flexibility in repaying their loans, more information about ... at a time when total outstanding student loan debt, including federal and private ...
(Date:4/29/2016)... ... April 29, 2016 , ... A ... born with severe congenital diaphragmatic hernia have better survival rates if surgery is ... hernia (CDH)—a condition where the diaphragm fails to form completely, letting abdominal organs ...
(Date:4/29/2016)... ... ... Mobility Designed is redefining mobility with their patent pending crutch design. ... distributes body weight from the elbow to the forearm. In consumer tests, users ... other crutches. , Co-founders Max and Liliana Younger were inspired to design the crutches ...
(Date:4/29/2016)... (PRWEB) , ... April 29, 2016 , ... Melanoma is the deadliest type of skin ... blame for the majority of skin cancer deaths. More than 10,000 people are expected to ... at diagnosis is 62, it is the one of the most commonly diagnosed cancers in ...
(Date:4/29/2016)... Hills, CA (PRWEB) , ... April 29, 2016 , ... ... of devices and products for the head and neck/ear, nose and throat specialty, has ... Device , The KOTLER NASAL AIRWAY™ is a newly patented safety device ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... YORK , April 28, 2016  While ... notably complement the company,s valve repair and stent ... move also places Abbott more firmly into patient ... of the fastest growing device areas, with double-digit ... its recent report,  Advanced Remote Patient Monitoring ...
(Date:4/28/2016)... YORK , April 28, 2016  The blood ... 275 million dollars, according to Kalorama Information and The ... typing, immunoassays and nucleic acid testing.  The healthcare research ... made progress in developing blood collection stations and in ... made in Kalorama Information,s report, Blood Testing ...
(Date:4/28/2016)... , April 28, 2016 Oramed ... a clinical-stage pharmaceutical company focused on the development of oral ... in the upcoming PIONEERS 2016 conference, presented by Joseph ... 2016 in New York . Nadav ... at the conference. Presentation Details:   ...
Breaking Medicine Technology: