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
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences