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 Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

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: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Laser use for neurosurgery and biofabrication - LaserForum 2016 focuses on medical technology

27.09.2016 | Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

 
Latest News

New switch decides between genome repair and death of cells

27.09.2016 | Life Sciences

Nanotechnology for energy materials: Electrodes like leaf veins

27.09.2016 | Physics and Astronomy

‘Missing link’ found in the development of bioelectronic medicines

27.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>