Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The mechanics of anti-tumor activity outlined

23.04.2003


Inhibiting the growth and the angiogenic properties of cancer is an important modality for cancer treatment and research. Angiogenesis, the development of new blood vessels from pre-existing vasculature, supports the development of many diseases including cancer, rheumatoid arthritis and others. In the case of cancer, angiogenesis is essential for the growth, progression and metastasis of a tumor and thus, agents that inhibit angiogenesis are attractive therapeutic options.



In an article published today in the April issue of Cancer Cell (Vol. 3, No. 4, pg. 363), Winship Cancer Institute (WCI) researchers report that 2-methoxyestradiol (2ME2) inhibits tumor growth and angiogenesis by suppressing hypoxia-inducible factor-1 (HIF). HIF is a factor that is over-expressed in more than 70% of human cancers and their metastases, including breast, prostate, brain, lung, and head and neck cancers.

Besides cancer, HIF is also associated with diseases of the bone and diseases that are mediated by inflammation such as rheumatoid arthritis.


The paper, "2ME2 Inhibits Tumor Growth and Angiogenesis by Disrupting Microtubules and Dysregulating HIF," was authored by WCI and EmoryUniversity scientists Nicola J. Mabjeesh, MD, PhD, Daniel Escuin, and Paraskevi Giannakakou, PhD. The paper was co-authored with scientists Theresa LaVallee, PhD, Victor Pribluda, PhD, and Glenn Swartz from EntreMed, a biopharmaceutical leader in angiogenesis research and product development.

2ME2 is a well-tolerated, orally active small molecule with anti-angiogenic and anti-tumor activity currently in Phase I/II clinical trials under the name PanzemÒ The trials are being conducted by EntreMed.

"This report contributes to the body of knowledge that will help us better understand the basic mechanism by which 2ME2 inhibits cancer cell growth and tumor angiogenesis," says Dr. Giannakakou.

Drs. Mabjeesh and Giannakakou report that 2ME2 inhibits tumor growth and angiogenesis by targeting microtubules, or a cell’s skeleton, and suppressing HIF activity.

"The study is the first to demonstrate that an agent, 2ME2, inhibits the assembly of microtubules in the tumors of treated animals," says Dr. Giannakakou. "Microtubule disruption results in the down regulation of HIF-1a. While this effect is not unique to 2ME2 when compared to Taxol or vincristine in preclinical models, it is the most more potent HIF inhibitor of all the microtubule-targeting chemotherapeutic agents tested that are used to treat cancer."

The paper outlines the mechanism by which 2ME2 downregulates HIF; a finding that had not been previously discovered. Utilizing a pharmacological approach and xenograft models, which are mouse models of human cancer, investigators showed that 2ME2 depolymerizes microtubules and blocks HIF-1a nuclear accumulation and HIF-transcriptional activity, or the transfer of genetic code information from one kind of nucleic acid to another.

"This research is important because we see for the first time a mechanistic link between targeting of the microtubule cytoskeleton and inhibition of angiogenesis," says Dr. Giannakakou. "This work will provide a new framework to study and develop novel compounds for the treatment of cancer."

In addition to Drs. Mabjeesh, and Giannakakou and PhD-candidate Daniel Escuin, WCI investigators Margaret T. Willard, PhD, Hua Zhong, PhD, and Jonathan Simons, MD contributed to the paper.

Vincent Dollard | EurekAlert!
Further information:
http://www.emory.edu/

More articles from Health and Medicine:

nachricht Spanish scientists create a 3-D bioprinter to print human skin
24.01.2017 | Carlos III University of Madrid

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General 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: Scientists spin artificial silk from whey protein

X-ray study throws light on key process for production

A Swedish-German team of researchers has cleared up a key process for the artificial production of silk. With the help of the intense X-rays from DESY's...

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Breaking the optical bandwidth record of stable pulsed lasers

24.01.2017 | Physics and Astronomy

Choreographing the microRNA-target dance

24.01.2017 | Life Sciences

Spanish scientists create a 3-D bioprinter to print human skin

24.01.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>