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 Electrical 'switch' in brain's capillary network monitors activity and controls blood flow
27.03.2017 | Larner College of Medicine at the University of Vermont

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>