New treatment proposed to prevent intestinal inflammation in cancer patients

This shows Prof. Yinon Ben-Neriah (left) and Naama Kanarek of the Hebrew University of Jerusalem Credit: The Hebrew University of Jerusalem

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.

Mucositis is a strong 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 , allowing 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 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 journal PNAS.

add to favorites email to friend print save as pdf

Related Stories

Slowing down the immune system when in overdrive

Feb 10, 2014

Many people suffer from chronic inflammation because their immune systems overreact to 'self' tissue. Sydney scientists believe that a small molecule known as Interleukin 21 is a promising therapeutic target in such cases.

Recommended for you

Diet affects men's and women's gut microbes differently

4 hours ago

The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a study by scientists from The University of Texas at Austin and six other institutions published ...

Researchers explore what happens when heart cells fail

5 hours ago

Through a grant from the United States-Israel Binational Science Foundation, Biomedical Engineering Associate Professor Naomi Chesler will embark upon a new collaborative research project to better understand ...

Stem cells from nerves form teeth

7 hours ago

Researchers at Karolinska Institutet in Sweden have discovered that stem cells inside the soft tissues of the tooth come from an unexpected source, namely nerves. These findings are now being published in the journal Nature and co ...

User comments