Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New approach by Cornell researcher could enable treatment of some cancers with retinoic acid with little or no side effects

14.08.2002


For some time doctors have been using a vitamin A derivative, retinoic acid (RA), to treat several cancers, particularly prostate cancer and leukemia, and they are now experimenting with the drug to treat breast cancer. The great drawback to RA, however, is that it requires high levels of the medication in order to turn genes "on" and "off," often triggering devastating and potentially fatal side effects.



Now, a Cornell University biochemist has learned how to make tumor cells up to 1,000 times more sensitive to RA so that much smaller doses would be required to flick the "on" and "off" switch (a process known as the induction of gene expression).

"This novel strategy for regulating the anticarcinogenic activity of retinoic acid has potential not only for treating tumors but also, perhaps, for protecting high-risk patients preventively," says Noa Noy, a professor of nutritional sciences at Cornell. "We have discovered that a naturally occurring protein in the cell can dramatically enhance the ability of RA to inhibit the proliferation of breast cancer cells, so that much less RA -- perhaps even the amount naturally present in the body -- is required to suppress tumor development."


The new findings are described in two recent articles in Molecular and Cellular Biology (April and July 2002).

RA belongs to a class of compounds known as retinoids that play key roles in regulating gene transcription and, therefore, govern multiple functions in the body, such as cell division and differentiation, immune response and embryonic development. They also control the development and spread of cancer cells, and some, including RA, can inhibit tumor growth by preventing cancer cell proliferation. Retinoids are now in clinical trials for treatment of head, neck and breast cancers, as well as for diabetes, arteriosclerosis and emphysema.

In the body, RA activates a protein in cells known as retinoic acid receptor (RAR) that binds to certain DNA sequences and turns target genes on or off. A typical treatment with RA seeks to activate RAR in order to switch on favorable genes. However, at pharmacological doses, RA and other retinoids are highly toxic. Moreover, cancer patients frequently become resistant to RA therapy over time.

Noy decided to take a different approach by seeking to understand how the gene-transcription activity of RA is regulated by two proteins called cellular retinoic acid-binding proteins (CRABP-I and CRABP-II). These proteins were identified decades ago, but their exact functions remained obscure.

"We have found that as soon as RA binds to CRABP-II, the protein rapidly moves into the cell nucleus, unlike CRABP-I, which keeps RA out of the nucleus. Once in the nucleus, CRABP-II binds to RAR and channels RA to it, thereby activating the transcription factor to turn genes on or off," explains Noy.

Noy has found that CRABP-II greatly enhances the transcriptional activity of retinoic acid receptors by directly targeting RA to them. Therefore, she has been working on introducing CRABP-II to cells to treat cancer. She is looking into patenting her approaches.

Noy also has indications that CRABP-II can slow tumor growth in the presence of very small amounts of RA. In new, as yet unpublished, research, Noy -- in collaboration with nutritional sciences colleague Danny Manor, and Rodney Page and Alexander Nikitin of Cornell’s College of Veterinary Medicine -- studied the effectiveness of CRABP-II in mice with cancer. When tumors in the mice reached half a centimeter, one group received injections of a virus that expressed CRABP-II in the tumors.

"The rate of growth of tumors in the mice that received CRABP-II was dramatically slower," says Noy. "The implication here is that we may not even need to administer RA to treat tumors, but can make use of the RA already present in the body and use CRABP-II to sensitize the tumor to it," she observes.

Noy hopes to perfect the technique so that researchers can develop an approach to introduce CRABP-II in specific tissues and thereby influence target-gene expression.

The research was supported, in part, by the National Institutes of Health, the Swiss National Science Foundation and the Novartis Foundation.

Susan S. Lang | EurekAlert!
Further information:
http://www.nutrition.cornell.edu/faculty/noy.html

More articles from Health and Medicine:

nachricht Fast-tracking T cell therapies with immune-mimicking biomaterials
16.01.2018 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht Dengue takes low and slow approach to replication
12.01.2018 | Duke University

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 decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

White graphene makes ceramics multifunctional

16.01.2018 | Materials Sciences

Breaking bad metals with neutrons

16.01.2018 | Materials Sciences

ISFH-CalTeC is “designated test centre” for the confirmation of solar cell world records

16.01.2018 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>