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 Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>