Navigation Links
Metabolic molecule drives growth of aggressive brain cancer
Date:6/13/2013

COLUMBUS, Ohio A study led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) has identified an abnormal metabolic pathway that drives cancer-cell growth in a particular glioblastoma subtype. The finding might lead to new therapies for a subset of patients with glioblastoma, the most common and lethal form of brain cancer.

The physician scientists sought to identify glioblastoma subtype-specific cancer stem cells. Genetic analyses have shown that high-grade gliomas can be divided into four subtypes: proneural, neural, classic and mesenchymal.

This study shows that the mesenchymal subtype is the most aggressive subtype, that it has the poorest prognosis among affected patients, and that cancer stem cells isolated from the mesenchymal subtype have significantly higher levels of the enzyme ALDH1A3 compared with the proneural subtype.

The findings, published recently in the Proceedings of the National Academy of Sciences, show that high levels of the enzyme drive tumor growth.

"Our study suggests that ALDH1A3 is a potentially functional biomarker for mesenchymal glioma stem cells, and that inhibiting that enzyme might offer a promising therapeutic approach for high-grade gliomas that have a mesenchymal signature," says principal investigator Ichiro Nakano, MD, PhD, associate professor of neurosurgery at the OSUCCC James. "This indicates that therapies for high-grade gliomas should be personalized, that is, based on the tumor subtype instead of applying one treatment to all patients," he says.

The National Cancer Institute estimates that 23,130 Americans will be diagnosed with brain and other nervous system tumors in 2013, and that 14,000 people will die of these malignancies. Glioblastoma accounts for about 15 percent of all brain tumors, is resistant to current therapies and has a survival as short as 15 months after diagnosis.

Little is known, however, about the metabolic pathways that drive the growth of individual glioblastoma subtypes knowledge that is crucial for developing novel and effective targeted therapies that might improve treatment for these lethal tumors.

For this study, Nakano and his collaborators used cancer cells from 40 patients with high-grade gliomas, focusing on tumor cells with a stem-cell signature. The researchers then used microarray analysis and pre-clinical animal assays to identify two predominant glioblastoma subtypes, proneural and mesenchymal.

Key technical findings include:

  • Genes involved in glycolysis and gluconeogenesis, particularly ALDH1A3, were significantly up-regulated in mesenchymal glioma stem cells compared to proneural stem cells;
  • Mesenchymal glioma stem cells show significantly higher radiation resistance and high expression of DNA-repair genes;
  • Radiation induces transformation of proneural glioma stem cells into mesenchymal-like glioma stem cells that are highly resistant to radiation treatment; inhibiting the ALDH1 pathway reverses this resistance.
  • Inhibiting ALDH1A3-mediated pathways slows the growth of mesenchymal glioma stem cells and might provide a promising therapeutic approach for glioblastomas with a mesenchymal signature.

"Overall, our data suggest that a novel signaling mechanism underlies the transformation of proneural glioma stem cells to mesenchymal-like cells and their maintenance as stem-like cells," Nakano says. Currently, their discoveries are in provision patent application, led by the Technology Licensing Office at University of Pittsburgh.


'/>"/>

Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

Related medicine news :

1. Metabolic PET imaging provides earlier warning of coronary disease
2. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Offer Improved hCG Diets to Counteract Metabolic Slowdown
3. Roundworm quells obesity and related metabolic disorders
4. Metabolic disorders predict the hardening of the arterial walls already in childhood
5. Epoxide hydrolase inhibition and Thiazolidinediones: A therapy for cardiometabolic syndrome
6. Monounsaturated fats reduce metabolic syndrome risk
7. Monosaturated fats reduce metabolic syndrome risk
8. Altman Fitness Launches the Metabolic Typing - Customized Nutrition Plan
9. EU funds research project on obesity and metabolic complications
10. Selexis SA Announces Publication in Metabolic Engineering of Data Demonstrating Improvement of Therapeutic Protein Secretion with Engineered CHO Cells
11. Recon 2 modeling may help tailor treatments for patients with metabolic diseases, cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... ... February 11, 2016 , ... The book, “Computers Should Just Work!”, provides a ... ask your IT consultant before signing a contract and how to spot an incompetent ... companies relying heavily on e-mail and technology, it’s more important than ever to make ...
(Date:2/11/2016)... ... ... As part of their 2015 end of year funding strategy, Colleen’s ... gifted $10,000 to University of Chicago to support ovarian cancer research being conducted by ... honored to support a promising young investigator from Dr. Lengyel’s lab at the University ...
(Date:2/10/2016)... ... February 10, 2016 , ... The 9th annual ... Imaging Congress (WMIC), will be held in New York City, NY on September ... Therapy.” The congress will highlight and emphasize how imaging reveals a greater understanding ...
(Date:2/10/2016)... New York, NY (PRWEB) , ... February 10, 2016 , ... ... a campaign to celebrate and raise awareness of Nestlé KITKAT as the first global ... improve the lives of cocoa farmers and the quality of their product, through activities ...
(Date:2/10/2016)... ... February 10, 2016 , ... ... a full-service health care communications company offering education, research and medical media, ... practitioners and specialists working in infectious diseases. , As the all-inclusive resource ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)...   Genomic Health, Inc. (Nasdaq: GHDX ) today ... ended December 31, 2015. --> --> ... compared with $69.1 million in the fourth quarter of 2014, an ... 9 percent compared with the same period in the prior year. ... $63.9 million in the fourth quarter of 2015, an increase of ...
(Date:2/10/2016)... Mylan N.V. (NASDAQ, TASE: MYL) today announced its financial ... --> --> Financial ... $9.45 billion, up 28% on a constant currency basis ... billion. Excluding the impact of the acquisition of Abbott ... (the "EPD Business"), full year adjusted total revenues increased ...
(Date:2/10/2016)... , Feb. 10, 2016 CSI Specialty ... with the launch of the Specialty Pharmacy Podcast. A ... industry-first, aimed at providing real-world education, discussion and context ... --> --> The Specialty ... CEO of CSI Specialty Group Suzette DiMascio, CHE, CMCE, ...
Breaking Medicine Technology: