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 Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>