Experimental work pointing to a therapy for alleviating mucositis -- a common, severe side effect of chemotherapy and irradiation of cancer patients or patients prepared for bone marrow transplantation – has been achieved by an international team of researchers from the US and Israel headed by scientists at the Hebrew University of Jerusalem.
Prof. Yinon Ben-Neriah (left) and Naama Kanarek
Mucositis is a strong inflammatory reaction of the mucosal lining of the digestive system, particularly the gut. Mucositis is often a major reason for premature suspension of anti-cancer therapy. As of today, there has been no effective means of preventing mucositis or its treatment.
The research group at the Hebrew University specializes in genetic engineering of mouse models (GEMMs) of inflammation and cancer. Naama Kanarek, a doctoral student at the Lautenberg Center for Immunology and Cancer Research and the Institute for Medical Research Israel–Canada at the Hebrew University Faculty of Medicine, constructed a mouse model designed to study the effect of deleting a gene encoding the enzyme beta-TrCP.
This enzyme was discovered in the laboratory of Hebrew University Prof. Yinon Ben-Neriah 15 years ago, in collaboration with the Israeli Nobel Laureate Prof. Aaron Ciechanover, as a major regulator of inflammatory cascades.
Kanarek found that beta-TrCP deletion in the gut causes mucosal DNA damage, mimicking the effect of chemotherapy and irradiation. Similarly to human patients, she showed that a severe mucositis reaction occurred in mice who were genetically engineered to be beta-TrCP-deficient.
Tracing the pathological basis of the mouse mucositis revealed that the source of the problem was Interleukin-1 (IL-1 beta), a protein secreted by the stressed mucosa. IL-1 beta was found to abnormally open the gut lining, allowing gut bacteria to penetrate and destroy the gut interior. Most importantly was Kanarek’s observation that treating the mice with an antibody which blocks IL-1 beta prevents the onset of mucositis in the beta-TrCP-deficient mice.
Based on these findings, the researchers proposed that IL-1b beta blocking reagents, like Anakinra (Kineret), which is used for treating certain chronic inflammatory conditions like rheumatoid arthritis and Crohn’s disease, should be tried for preventing mucositis in humans.
The work of the researchers was published recently in the American journal PNAS.
(A higher resolution version of this photo is available via e-mail upon request)
CONTACT:Jerry Barach, Hebrew University Foreign Press Liaison
Jerry Barach | Hebrew University
Penn study identifies viral product that promotes immune defense against RSV
04.09.2015 | University of Pennsylvania
Columbia Engineering team develops targeted drug delivery to lung
03.09.2015 | Columbia University School of Engineering and Applied Science
In a survey of NASA's Hubble Space Telescope images of 2,753 young, blue star clusters in the neighboring Andromeda galaxy (M31), astronomers have found that M31 and our own galaxy have a similar percentage of newborn stars based on mass.
By nailing down what percentage of stars have a particular mass within a cluster, or the Initial Mass Function (IMF), scientists can better interpret the light...
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE have developed a highly compact and efficient inverter for use in uninterruptible power...
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists. The study is the first to explain how the steep-fronted plateau formed.
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from...
The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.
Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...
Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.
"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...
03.09.2015 | Event News
20.08.2015 | Event News
20.08.2015 | Event News
04.09.2015 | Power and Electrical Engineering
04.09.2015 | Machine Engineering
04.09.2015 | Materials Sciences