Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a leading cause of cancer-related deaths worldwide. Although there are several treatment options available, they are largely unsuccessful because the disease is so poorly understood.
Clinical studies of patients with HCC, combined with studies using mice and other animal models, have provided some clues, but many questions about how to diagnose and treat this deadly form of cancer remain. Zhiyuan Gong and Serguei Parinov from the National University of Singapore decided to pursue these questions using zebrafish as a model system.
Their study uncovers new information that might help to diagnose and treat HCC in humans, and shows that zebrafish are a powerful and cost-effective model to study liver cancer. Gong and Parinov publish their results in Disease Models & Mechanisms on July 5th, 2011 at http://dmm.biologists.org/.
Previous work indicated that cancer cells from patients with HCC always have abnormally high activation of a cellular pathway called Ras. However, whether and how the Ras pathway actually causes liver cancer was not clear. To focus in on this issue, Gong and Parinov generated zebrafish that are genetically engineered to express a cancer-causing form of Ras (krasV12) in the liver.
Fish that had the highest expression of krasV12 all died rapidly of malignant liver cancer (mostly within 30 days), whereas fish with lower krasV12 expression survived for longer and did not develop full-blown liver cancer. These results suggest that only very high levels of Ras pathway activation can cause HCC.
The researchers also uncovered abnormalities in several other cellular pathways in zebrafish that developed liver cancer, and genetic studies confirmed that the progression of disease happens similarly in zebrafish and humans. This allowed the researchers to establish a 'genetic signature' for HCC, which could potentially be translated into a method for diagnosing the disease in humans. In addition, the stage of cancer is an important factor in determining how patients should be treated. In this study, the researchers determined genetic signatures that were specific to early- and late-stage liver cancer, which might help in planning treatment regimes for patients with HCC.
These new findings using a zebrafish model of HCC should help to guide studies of this complex cancer in humans. Although validation studies in patients with HCC are required, this work provides new evidence that drugs targeting the Ras pathway are a promising avenue for therapy.
IF REPORTING ON THIS STORY, PLEASE MENTION DISEASE MODELS & MECHANISMS AS THE SOURCE AND, IF REPORTING ONLINE, PLEASE CARRY A LINK TO: http://dmm.biologists.org/
REFERENCE: Nguyen, A. T., Emelyanov, A., Koh, C. H. V., Spitsbergen, J. M., Lam, S. H., Mathavan, S., Parinov, S. and Gong, Z. Dis. Model. Mech. doi:10.1242/dmm.007831
This article is posted on this site to give advance access to other authorised media who may wish to report on this story. Full attribution is required, and if reporting online a link to dmm.biologists.com is also required. The story posted here is COPYRIGHTED. Therefore advance permission is required before any and every reproduction of each article in full. PLEASE CONTACT email@example.com
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction