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 New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's 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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>