One focus of attack is a chemical pathway within stem cells known as Notch, which scientists have shown is important for cancer stem cell growth. A new study published in the January 28 issue of Stem Cells by Charles Eberhart, M.D., Ph.D., associate professor of pathology, ophthalmology, and oncology at Johns Hopkins, now extends these findings to glioblastoma, the most common malignant brain tumor, and ultimately suggests other pathways and treatment with two or more drugs may need to be involved.
Eberhart based his conclusion on experiments in which he coaxed a glioblastoma cell line to form embryolike balls called neurospheres. Unlike most cells that will clump together in a culture dish, neurospheres – more organized groups of neural cells – can only form from stem cells. When Eberhart treated the neurospheres with a drug called GSI-18, which blocks the Notch pathway, the spheres were reduced by 70 percent or more. Eberhart also found that molecular markers typically found on the surface of brain cancer stem cells also plunged.
“This told us that the Notch pathway is a good target for drug development,” says Eberhart, but further experiments suggested this approach may not be thorough enough.
In a second set of experiments, Eberhart collected the neurospheres that remained after treatment with the Notch-blocking drug and injected them into the brains of mice. The neurosphere transplants eventually grew into tumors and reignited the Notch pathway.
“This result suggested we didn’t get rid of all the stem cells,” says Eberhart, “so it’s likely we may need to add more therapies or increase the dosage of Notch-blocking drugs.”
The study by Eberhart identified additional molecular pathways, including Stat 3 and AKT, which are connected to Notch. He says that a combination of therapies blocking Notch and other pathways such as these could target brain cancer stem cells at several levels and possibly avoid drug resistance.
To test how a Notch-blocking drug worked in an animal model, Eberhart injected tumors into the brains of mice and let the cancer grow for two weeks. Then, at the tumor site, he implanted a polymer bead that was soaked in GSI-18. Five of six mice that received the drug-laden bead survived while all 12 that received a bead with no drug died.
Eberhart notes that Notch-targeting drugs can prove problematic in therapy because the Notch pathway is critically important for cells in the gut, helping cells there alternate between secreting mucus and absorbing nutrients. “A dosing regimen that preserves gut function has been developed, and forthcoming studies in humans will test whether it can kill the cancer stem cells.”
Funds for this research were provided by the Accelerate Brain Cancer Cure Project Award, the American Brain Tumor Association, Voices Against Brain Cancer Research, the National Institutes of Health, and the Brain Tumor Funders Collaborative.
Research participants include Xing Fan, Thant S. Zhu, Mary E. Soules, and Caroline E. Talsma from the University of Michigan; Leila Khaki, Naheed Gul, Cheryl Koh, and Jiangyang Zhang from Johns Hopkins; Yue-Ming Li from Memorial Sloan-Kettering Cancer Center; Jarek Maciaczyck and Guido Nikkhah from the University of Freiberg; and Francesco DiMeco, Sara Piccirillo, and Angelo L. Vescovi from the University of Milan.Media Contact: Vanessa Wasta
Vanessa Wasta | EurekAlert!
NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)
High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
20.11.2017 | Earth Sciences
20.11.2017 | Earth Sciences
20.11.2017 | Life Sciences