Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Radiation helps drugs ’zero in’ on tumor blood vessels

21.01.2003


Technique used to shrink tumors, delay their growth



A team of Vanderbilt-Ingram Cancer Center scientists shrunk tumors or delayed their growth in animal studies by using radiation to enable a drug to "zero in" and block the tumor blood vessels.

The work, reported in the January issue of the journal Cancer Cell, is a model for what might be achieved in patients by using radiation to activate drug targets in tumors. "We can now use combinations of chemotherapy and radiation to improve the anti-cancer effect for many of our patients, but the side effects can be great," said Dr. Dennis Hallahan, chair of Radiation Oncology at Vanderbilt- Ingram. "With this approach, we hope we can ultimately deliver drugs directly and selectively to the tumor alone, and reduce side effects."


This paper describes work by investigators in Vanderbilt’s departments of Radiation Oncology, Radiology, Biochemical Engineering and Cancer Biology to identify receptors in tumor blood vessels that are activated by radiation and then to demonstrate that these receptors can be selectively targeted.

To identify the radiation-induced targets, the scientists treated tumor- bearing animals with radiation and then injected them with a peptide library. The peptides (portions of proteins) that correspond to the radiation-induced receptors bind, or stick, and can then be recovered. By identifying which peptides stick to radiation-treated tumor cells compared to untreated cells, the scientists can identify what receptors are activated by radiation.

A particular protein portion, the amino acid sequence RGDGSSV, was recovered from several tumor models and was found to bind within the tumor blood vessels. It was found to bind to two types of fibrinogen receptors that are important to angiogenesis, the development of blood vessels. Tumor blood vessels are an attractive therapeutic target because tumor cells depend on the blood vessels for vital oxygen and nutrients necessary for their growth and spread.

The scientists then coated liposomes (fatty molecules that can be used to deliver drugs) with an antibody that binds to these fibrinogen receptors. These liposomes were tagged with a fluorescent marker so they could be tracked in the body and were injected into mice with tumors on both hind legs. The right tumors were treated with radiation, while the left tumors were left untreated as controls. The fluorescent marker, indicating the presence of the antibody-coated liposomes, was seen in the treated tumors but not in the untreated tumors. The finding suggests that anti-cancer drugs might be attached to these antibody-coated liposomes and targeted specifically to tumors.

The scientists next tested whether they could affect tumor growth by targeting these radiation-induced receptors with nanoparticles designed to obstruct the blood flow within the vessels. They compared effects of radiation combined with nanoparticles coated with the fibrinogen antibody versus radiation alone and radiation combined with uncoated nanoparticles.

Sonographic measurement of microscopic blood flow found that radiation alone or used with uncoated nanoparticles achieved virtually no change in tumor blood flow. However, blood flow was reduced by 85 percent in tumors treated with coated nanoparticles and radiation.

In addition, tumor growth was significantly delayed in tumors treated with radiation and coated nanoparticles, compared to those treated with uncoated nanoparticles or radiation alone.

Hallahan and his colleagues have begun pilot studies in cancer patients to test the feasibility of this approach. Current trials are designed to demonstrate that radiation can activate receptors in these patients that can then be targeted with the antibodies. Among the factors being explored are whether the type of radiation -- traditional external radiation, internally delivered radiation (brachytherapy) or stereotactically delivered radiation -- makes a difference in the ability to target therapy.

Hallahan estimates that clinical trials using this approach to test treatments are still several years away.


In addition to Hallahan, authors on the paper were Ling Geng, Shimian Qu, Christopher Scarfone, Todd Giorgio, Edwin Donnelly, Xiang Gao and Jeff Clanton.

The work was funded by the National Institutes of Health, including support from Vanderbilt-Ingram’s SPORE (Specialized Program Of Research Excellence) in Lung Cancer grant from the National Cancer Institute; the American Society for Therapeutic Radiation Oncology; and Vanderbilt’s department of Radiation Oncology.

Cynthia Manley | EurekAlert!
Further information:
http://www.mc.vanderbilt.edu/reporter/

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

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: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>