Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

10 Oct 2016 - 12 Oct 2016
12 Nov 2016 - 16 Nov 2016

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

By BiotechDaily International staff writers
Posted on 04 Mar 2014
Print article
The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients.

Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may slough off, and then become red, inflamed, and ulcerated. Ulcers may range from 0.5 centimeters to greater than four centimeters. Oral mucositis can be severely painful with the degree of pain usually related to the extent of the tissue damage. Due to pain, the patient may experience trouble speaking, eating, or even opening the mouth. Mucositis is often a major reason for premature suspension of anticancer therapy.

To study the molecular mechanisms responsible for mucositis investigators at the Hebrew University of Jerusalem (Israel) genetically engineered a line of mice to lack the gene that encodes the enzyme E3 beta-TrCP (beta-transducin repeat containing E3 ubiquitin protein ligase) in their gut epithelium. Deletion of beta-TrCP in the gut deregulated the cell cycle, induced a DNA damage response (DDR), and abolished the epithelium barrier function, resulting in a lethal mucosal inflammation that mimicked human mucositis.

Examination of these animals at the molecular level revealed that epithelial-derived IL-1beta, likely induced by DDR independently of NF-kappaB, was a major culprit, and initiated the pathology by compromising epithelial tight junctions. IL-1beta is a member of the interleukin 1 family of cytokines. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1. This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 by this cytokine in the central nervous system was found to contribute to inflammatory pain hypersensitivity.

The investigators reported in the January 27, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that antibody neutralization of IL-1beta prevented epithelial tight junction dysfunction and alleviated mucositis in beta-TrCP–deficient mice. They suggested that IL-1beta antagonists should be considered for prevention and treatment of mucositis.

Related Links:

Hebrew University of Jerusalem 




Print article

Channels

Drug Discovery

view channel
Image: Ginger is the source of a novel class of nanolipid transport vector (Photo courtesy of Georgia State University).

Ginger-Derived Doxorubicin-Loaded Nanovectors as Drug Delivery for Cancer Therapy

A novel type of nanoparticle drug transport system based on lipids isolated from ginger was used to deliver the toxic chemotherapeutic agent doxorubicin (Dox) to colon cancer cells with minimal damage... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.