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!
Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)
Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
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...
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.
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...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences