Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson researchers identify critical marker of response to gemcitabine in pancreatic cancer

08.06.2009
A protein related to aggressive cancers can actually improve the efficacy of gemcitabine at treating pancreatic cancer, according to a Priority Report in Cancer Research, published by researchers at Thomas Jefferson University.

The protein, called Hu antigen R (HuR), is a stress response protein found in the cytoplasm of pancreatic tumor cells. In certain experimental settings, pancreatic cancer cells that overexpressed HuR were up to 30-fold more sensitive to gemcitabine (Gemzar), according to Jonathan Brody, Ph.D., assistant professor of Surgery at Jefferson Medical College of Thomas Jefferson University.

In a clinical correlate study that included 32 resected pancreatic cancer patients who received gemcitabine, patients who had low cytoplasmic HuR levels had a 7-fold increased mortality risk compared to patients with high levels. This was after adjustment for other variables including age, sex, radiation therapy and other chemotherapy use.

"This marker appears to tell us upfront whether a patient will respond to treatment with gemcitabine, which is the routine treatment for pancreatic cancer," said Dr. Brody, who is the senior author of the study. "Of course, larger and comprehensive prospective studies need to be performed, but we now have a real clue about how to make this treatment better. Finding a mechanism that regulates gemcitabine's metabolism in pancreatic cancer cells is the real novel and exciting aspect of these findings."

Dr. Brody and colleagues found that in pancreatic cancer, HuR helps to regulate an enzyme called deoxycytidine kinase (dCK), which is responsible for metabolizing and activating gemcitabine. As with most chemotherapy drugs, gemcitabine causes cell stress and activates the HuR stress proteins. In turn, the high levels of HuR stimulate the production of more dCK, thus making gemcitabine more efficient, according to Dr. Brody.

"Normally, patients higher HuR cytoplasmic levels have a worse prognosis, since HuR expression is associated with advanced malignancies," Dr. Brody said. "However, in our study, they did better than patients with low HuR levels when they were treated with gemcitabine. We think it's because they already have high HuR levels at the time of treatment, which may be a response to the tumor cell environment."

According to Dr. Brody, research is underway to find a way to activate HuR in patients with a low expression. Other goals include expanding these findings to a larger pancreatic cancer population, and to other tumors that may be treated with gemcitabine, including breast, ovarian and certain lung cancers. They also want to determine if other chemotherapeutic agents engage this intriguing and manipulative pathway.

Co-authors of the paper include Charles J. Yeo, M.D., Samuel D. Gross Professor and chairman of the department of Surgery, and Agnieszka Witkiewicz, M.D., assistant professor of Pathology, Anatomy and Cell Biology. Drs. Brody, Yeo and Witkiewicz are co-directors of the Jefferson Pancreas, Biliary and Related Cancer Center.

Other study collaborators include Dr. Myriam Gorospe from the National Institute on Aging (NIH) and Dr. Judith Keen from the University of Medicine and Dentistry of New Jersey.

Emily Shafer | EurekAlert!
Further information:
http://www.jefferson.edu

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>