Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Widely used anti-nausea drug may interfere with cancer chemotherapy

03.03.2004


A drug widely used to prevent nausea and other side effects in patients receiving chemotherapy for breast cancer may also, unfortunately, prevent the therapy from working efficiently on tumor cells, researchers from the University of Chicago report in the March 1 issue of the Journal, Cancer Research.



Dexamethasone, a synthetic steroid, is routinely given to women just before they receive chemotherapy with either paclitaxel or doxorubicin, two drugs commonly used to treat breast cancer. In this laboratory study, the researchers show that pretreatment with dexamethasone reduces the ability of paclitaxel and doxorubicin to kill cancer cells.

"Nearly every patient receiving chemotherapy for breast cancer also receives dexamethasone pre-treatments that may make therapy less effective," said Suzanne Conzen, M.D, assistant professor of medicine at the University of Chicago and director of the study. "With breast cancer one wants the best tumor reduction possible, but we have evidence that the benefits provided by routine treatment with dexamethasone may cause decreased chemotherapy-induced tumor cell death."


Conzen’s team became suspicious nearly four years ago when they discovered that a group of steroid hormones know as glucocorticoids could inhibit death in certain cell types, including breast epithelial cells. This made them begin to question the wisdom of treating breast cancer patients with dexamethasone (known as Dex), an artificial glucocorticoid.

A careful search of the literature on dexamethasone uncovered another surprise. "Remarkably," the authors note, no clinical studies had ever addressed the potential effects on tumor response of administering Dex before routine chemotherapy for breast cancer.

To study these effects at the molecular level, Conzen’s team devised a laboratory system that mimicked the usual clinical administration of dexamethasone in this setting. They found that pretreatment of breast cancer cells with dexamethasone reduced the cell death rate following exposure to either paclitaxel or doxorubicin by more than 25 percent, even though the two drugs rely on very different mechanisms to cause tumor cell destruction.

Since dexamethasone actually kills certain types of cells such as lymphocytes and is effective treatment for lymphoma, the researchers wondered why Dex destroys one type of cancer cell yet protects another from cell death. Using a technique that measures the effects of a drug on gene expression, they found that dexamethasone consistently upregulated 45 genes in breast cancer cells and that these genes differed from those found to be regulated by dexamethasone in earlier studies using lymphocytes.

They then focused their attention on two genes that were upregulated in breast cells by dexamethasone -- SGK-1 and MKP-1. SGK-1 has been previously shown to prevent cell death in brain and breast cells. MKP-1 can protect prostate cancer cells and its increased expression is associated with breast, ovarian and pancreatic cancers.

They found that both SGK-1 and MKP-1 played a major role in dexamethasone’s effects, protecting breast cancer cells from the effects of both paclitaxel and doxorubicin. Blocking these proteins, on the other hand, reversed the drug’s unwanted effects on cancer cell survival.

Although the authors are not yet ready to stop using dexamethasone, a very effective drug for prevention of side effects from chemotherapy, Conzen suggests that the evidence is mounting that oncologists "should begin to study the effects of using this drug routinely as part of breast cancer therapy."

"The widespread use of drugs such as dexamethasone before chemotherapy," the authors conclude, "requires reevaluation because of the observed inhibition of chemotherapy efficacy."

Additional authors of the study were Wei Wu, Shamita Chaudhuri, Deanna Brickley, Diana Pang and Theodore Karrison of the University of Chicago. The National Institutes of Health, the Department of Defense, the Schweppe, Concern, Entertainment Industry and the University of Chicago Cancer Research Foundations supported the research.

John Easton | EurekAlert!
Further information:
http://www.medcenter.uchicago.edu/

More articles from Health and Medicine:

nachricht Candidate Ebola vaccine still effective when highly diluted, macaque study finds
21.10.2019 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Autism spectrum disorder risk linked to insufficient placental steroid
21.10.2019 | Children's National Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Solving the mystery of quantum light in thin layers

A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)

It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...

Im Focus: An ultrafast glimpse of the photochemistry of the atmosphere

Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.

The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...

Im Focus: Shaping nanoparticles for improved quantum information technology

Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.

Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...

Im Focus: Novel Material for Shipbuilding

A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.

The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...

Im Focus: Controlling superconducting regions within an exotic metal

Superconductivity has fascinated scientists for many years since it offers the potential to revolutionize current technologies. Materials only become superconductors - meaning that electrons can travel in them with no resistance - at very low temperatures. These days, this unique zero resistance superconductivity is commonly found in a number of technologies, such as magnetic resonance imaging (MRI).

Future technologies, however, will harness the total synchrony of electronic behavior in superconductors - a property called the phase. There is currently a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

NEXUS 2020: Relationships Between Architecture and Mathematics

02.10.2019 | Event News

Optical Technologies: International Symposium „Future Optics“ in Hannover

19.09.2019 | Event News

 
Latest News

Fraunhofer LBF and BAM develop faster procedure for flame-retardant plastics

21.10.2019 | Materials Sciences

For EVs with higher range: Take greater advantage of the potential offered by lightweight construction materials

21.10.2019 | Materials Sciences

Benefit and risk: Meta-analysis draws a heterogeneous picture of drug-coated balloon angioplasty

21.10.2019 | Medical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>