Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

By BiotechDaily International staff writers
Posted on 04 Mar 2014
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 




WATERS CORPORATION

Channels

Genomics/Proteomics

view channel
Image: Electron micrograph of Hepatitis C virus purified from cell culture. Scale bar is 50 nanometers (Photo courtesy of the Center for the Study of Hepatitis C, the Rockefeller University).

Oxidized LDL Predicts Response to Interferon Treatment of Chronic Hepatitis C and May Be a Treatment Option

Oxidized low-density lipoprotein (oxLDL) in the blood was shown to predict responsiveness to interferon treatment in patients with chronic Hepatitis C virus (HCV) infection and to inhibit spread of the... Read more

Drug Discovery

view channel
Image: Molecular model of the anti-cancer drug 5-fluorouracil (Photo courtesy of Wikimedia Commons).

Novel Microcapsule Approach Reduces Toxic Side Effects of Chemotherapy

Cancer researchers have reduced chemotherapy's toxic side effects by using nanoporous capsules to transport an enzyme to the site of a tumor where it is activated by a selective heating process to convert... Read more

Lab Technologies

view channel
Image: The gene assembly robot, the GeneTheatre (Photo courtesy of Analytik Jena AG).

Genomic Research Laboratories Await New Compact Liquid Handling System

A small footprint benchtop liquid handler that automates multiple gene assembly tasks and associated procedures such as PCR setup is now available for use by biotech and genomic research laboratories.... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 

Events

02 Jun 2015 - 03 Jun 2015
15 Jun 2015 - 18 Jun 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.