Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Identify Genes Linked to Chemoresistance

23.07.2009
Two genes may contribute to chemotherapy resistance in drugs like 5-fluorouracil, which is used in liver cancer treatment, according to Virginia Commonwealth University Massey Cancer Center researchers.

Liver cancer is a highly aggressive form that has limited therapeutic options. One of the key challenges with cancer treatment is that patients can develop resistance to chemotherapy. Researchers are examining ways to prevent resistance by determining the molecular mechanisms involved with cancer progression, and then developing new generations of chemotherapeutic agents.

In the study, published online in the Early Edition of the Proceedings of the National Academy of Sciences the week of July 13, researchers reported that two genes - astrocyte elevated gene-1, or AEG-1, and late SV40 factor, LSF, contribute to resistance of a commonly used chemotherapeutic drug called 5-fluorouracil, or 5-FU. The team found that over-expression of AEG-1 increased resistance of the liver cells to 5-FU. They observed that a second gene, LSF, is under the control of AEG-1 and mediates a series of molecular pathways involved the resistance to 5-FU.

Previous studies suggest that the expression of AEG-1, is very low in normal cells or tissues such as breast, prostate, liver and brain. However, in cancers of the same organs, expression of AEG-1 is significantly increased. AEG-1 was initially cloned in the laboratory of Paul B. Fisher, Ph.D., director of the VCU Institute of Molecular Medicine.

Earlier this year, the team determined that AEG-1 modulates expression of genes relevant to the progression of liver cancer, including invasion, metastasis, resistance to chemotherapy, the formation of new blood vessels and senescence. They identified that LSF, a transcription factor that regulates gene expression, is increased by AEG-1.

“Since AEG-1 is a key regulator of liver cancer development and progression, understanding how this molecule works will provide profound insights into the mechanism of liver cancer development,” said principal investigator Devanand Sarkar, Ph.D., a Harrison Endowed Scholar in Cancer Research at the VCU Massey Cancer Center and assistant professor in the Department of Human and Molecular Genetics in the VCU School of Medicine.

“By understanding these molecular pathways and mechanisms, we may be able to create new drugs to inhibit the expression of AEG-1 or LSF and even develop combination drug therapies to enhance the effectiveness of 5- fluorouracil.”

“These findings may have important therapeutic implications. Based on the expression level of AEG-1 or LSF in tumor biopsy samples, a clinician might determine whether a patient would respond to 5-fluorouracil and thus design an effective chemotherapeutic protocol,” he said.

Sarkar said that AEG-1 contributes to resistance to not only 5-FU, but also to other chemotherapeutics such as doxorubicin and cisplatin, although the molecular mechanism of resistance to the latter drugs is different from 5-FU. The team is currently conducting studies to further understand the molecular mechanisms by which AEG-1 induces resistance to chemotherapy so that this knowledge might be applied to develop strategies to maximize the efficacy of chemotherapeutics. Additionally, novel combinatorial treatment approaches that incorporate AEG-1 or LSF inhibition in a standard chemotherapeutic protocol will be evaluated for their efficacy in inhibiting liver cancer in animal models.

This work was supported by grants from The Goldhirsh Foundation, the National Institutes of Health, and the Dana Foundation.

Sarkar worked with a team that included VCU School of Medicine researchers Byoung Kwon Yoo, Ph.D., Zao-zhong Su, Ph.D., Rachel Gredler, B.S., Nicollaq Vozhilla, D.V.M., Dong Chen, B.S., and Paul B. Fisher, M.Ph., Ph.D. Also contributing were Talitha Forcier, B.S., and Khalid Shah, Ph.D., from Harvard Medical School; and Utsav Saxena, and Ulla Hansen, Ph.D., from Boston University. The VCU Institute of Molecular Medicine also provided support in conducting these studies.

About VCU and the VCU Medical Center:

Virginia Commonwealth University is the largest university in Virginia with national and international rankings in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls 32,000 students in 205 certificate and degree programs in the arts, sciences and humanities. Sixty-five of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 15 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.

About the VCU Massey Cancer Center:

The VCU Massey CancerCenter is one of 63 National Cancer Institute-designated institutions that leads and shapes America’s cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers more clinical trials than any other institution in Virginia, serving patients in Richmond and in four satellite locations. Treating all kinds of cancers, its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and, ultimately, to cure cancer. Visit Massey online at www.massey.vcu.edu or call 1-877-4-MASSEY.

Sathya Achia Abraham | EurekAlert!
Further information:
http://www.vcu.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

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

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | 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

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>