Navigation Links
Cell-death receptor links cancer susceptibility and inflammation

PHILADELPHIA - For over 10 years, Wafik S. El-Deiry, MD, PhD, Professor of Medicine, Genetics, and Pharmacology at the University of Pennsylvania School of Medicine, has been pursuing a cancer-targeting molecule called TRAIL and its molecular partners. TRAIL is normally produced by immune cells and curtails tumor spread by binding to a specialized receptor on a tumors surface.

However, in cancer patients who often have suppressed immunity, and for reasons we still dont understand, there isnt enough TRAIL being produced, so tumors are not suppressed, explains El-Deiry, who is also Co-Program Leader of the Radiation Biology Program for the Abramson Cancer Center at Penn.

Most recently, El-Deiry and colleagues demonstrated for the first time a link between TRAILs receptor and cancer susceptibility, as reported online December 13, 2007 in the Journal of Clinical Investigation in advance of the January 2008 print issue. Unexpectedly, they also found a connection via Trail between inflammation and cancer susceptibility.

Mice engineered without the TRAIL receptor on their cells versus healthy controls developed larger and more tumors in their livers and other organs after being challenged with a chemical carcinogen or radiation. The team also bred TRAIL receptor knock-out mice with mice genetically engineered to get B-cell lymphomas that metastasize to the liver. Their offspring displayed more liver tumors compared to controls. This is the first direct in vivo evidence that loss of the tumor death-inducing TRAIL receptor confers cancer susceptibility, says El-Deiry.

When intact, TRAIL and its receptor decrease the influx of inflammatory cells and molecules that can lead to cancer. New models of cancer have suggested a link between inflammation and cancer in the last five years, and El-Deiry is in the early stages of trying to understand this connection with respect to the TRAIL pathway.

For example, in this study, the mice without the TRAIL receptor that were irradiated developed chronic pneumonia, an inflammatory response, as well tumors, evidence pointing to the connection between cancer and inflammation via TRAIL. One benefit of this work is that it provides a new and unanticipated model implicating a TRAIL pathway deficiency in the chronic toxicity of radiation therapy, he notes. Inflammation is a common late and serious side-effect of radiation treatment in people.

El-Deiry and his team are now looking within tumor tissue for inflammatory molecules as clues to how cancer and inflammation are coupled. Our work with TRAIL and its receptor in mouse models represents a new way to look at cancer susceptibility and its potential therapy in humans as well as new ways to decrease debilitating radiation side-effects experienced by cancer patients, says El-Deiry.

Co-authors in addition to El-Deiry are Niklas Finnberg from Penn and Andres J.P. Klein-Szanto from Fox Chase Cancer Center, Philadelphia. This research was funded in part by the National Cancer Institute.

This release can be found at

Contact: Karen Kreeger
University of Pennsylvania School of Medicine

Related medicine news :

1. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
2. Low level of neuronal receptor linked to mild cognitive impairment and Alzheimers disease
3. Pathway Diagnostics Announces Commercial Availability of SensiTrop(TM) HIV Co-receptor Tropism Assay
4. Pharmacopeia Acquires Selective Androgen Receptor Modulator (SARM) Program from Bristol-Myers Squibb
5. Food restriction increases dopamine receptor levels in obese rats
6. Quest Diagnostics Licenses Technology Underlying SensiTrop(TM) HIV Co-Receptor Tropism Test from Pathway Diagnostics
7. Abbott Researchers Target Neuronal Nicotinic Receptors for Treatment of Pain and Cognition
8. Exelixis to Receive Milestone Payment From Bristol-Myers Squibb for Achievement of Liver X Receptor Agonist Development Milestone
9. Receptor protein appears to be key in breakdown of kidney filtration
10. Pathway links inflammation, angiogenesis and breast cancer
11. Research Links TV/Video Game Playing With Child Obesity; Health Experts Back a New Approach
Post Your Comments:
(Date:12/1/2015)... , ... December 01, 2015 , ... ... leadless pacemakers in the U.S. and is the only hospital in the region ... largest clinical data presentation of transcatheter pacing patients were revealed recently at a ...
(Date:12/1/2015)... ... December 01, 2015 , ... Growth in medical payments per workers’ compensation claim ... of hospital and nonhospital care, according to a recent study by the Workers Compensation ... Edition , found medical payments per claim with more than seven days of lost ...
(Date:12/1/2015)... ... 01, 2015 , ... It’s official: Tattoo taboo is a thing of the ... among Millennials (a whopping one in three aged 18 to 25 is inked). As ... with their ink. In fact, RealSelf , the world’s largest community for learning ...
(Date:12/1/2015)... ... December 01, 2015 , ... For many X-rays taken at ... accurate interpretation by the radiologist. The marking utensils are so small, however, they ... found a way to alleviate this problem. , He developed the patent-pending MARK ...
(Date:12/1/2015)... ... December 01, 2015 , ... ... been selected as a finalist in this year’s Fierce Innovation Awards: Healthcare Edition, ... Healthcare was recognized as a finalist in the category of Digital Solutions for ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... Breg, Inc ., a premier provider ... it has been awarded three contracts by Novation, a ... will have access to improved pricing for Breg,s portfolio ... goods dedicated to advancing orthopedic care.  ... population, rising prevalence of chronic conditions and the health ...
(Date:12/1/2015)... 2015 During the recent 2015 Transcatheter ... Francisco, CA , Medinol Ltd. continued to ... During a satellite symposium, "The BioNIR eDES: The ... Restenosis", a renowned physician panel discussed the key ... Coronary Stent System and the Medinol eDES Coronary ...
(Date:12/1/2015)... 2015 ... of the "2016 Europe Enteric ... Coli, Enterovirus, Rhinovirus, Rotavirus, Salmonella, Shigella, ... offering. --> ) ... "2016 Europe Enteric Disease Testing ...
Breaking Medicine Technology: