Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UF oncologists fight leukemia with two-pronged therapy, clinical trials planned

04.06.2010
A new therapy mounts a double-barreled attack on leukemia, targeting not just the cancer cells but also the environment in which those cells live and grow, University of Florida researchers report.

Like striking an enemy camp directly as well as cutting off its source of food and other resources, the agent, called Oxi4503, poisons leukemia cells and destroys the blood vessels that supply them with oxygen and nutrients.

Use of the treatment in mouse models of acute myelogenous leukemia, or AML, is described online and in an upcoming print issue of the journal Blood. The researchers plan human tests of the drug at Shands at UF later this year.

"We've identified a new tool to dissect out the specifics of the relationship between leukemia cells and the blood vessels that supply them," said Christopher Cogle, M.D., the UF College of Medicine oncologist who is senior author of the paper and a member of the UF Shands Cancer Center. "What we are offering is a brand new treatment by a very different mechanism to people who desperately need something new."

Each year, more than 120,000 people in the United States are diagnosed with a blood cancer, and about 80 percent of them die of the disease because there are no effective treatments, according to the National Cancer Institute. Some AMLs return after initially successful chemotherapy, while others do not respond at all. In addition, chemotherapy is too toxic for some elderly people, so they need an alternative.

Many treatments and studies focus on killing cancer cells, but very few target the microenvironment in which those cells grow. That means paying attention to blood vessels, bone marrow, growth factors and cell-to-cell interaction and binding.

Existing therapies that destroy blood vessels do so by targeting a growth factor called VEGF-A, but they are not effective long term at eliminating leukemia. To try to find a strategy that attacked multiple targets, the researchers tested Oxi4503, a novel blood vessel-disrupting agent.

In mouse models, Oxi4503 killed leukemia cells in addition to destroying the blood vessels that fed and nurtured them.

"It is very exciting to find one drug that can target both the leukemic cell and the endothelium to diminish the progression of leukemias — those people who fail chemotherapy, early or late, could be treated with this drug to see whether they respond," said Shahin Rafii, M.D., a Howard Hughes Medical Institute Investigator and director of the Ansary Stem Cell Institute at Weill Cornell Medical College, who showed that leukemia cells are dependent on activated bone marrow blood vessels for survival and proliferation. Rafii is not affiliated with the UF study.

After Oxi4503 treatment, however, the researchers found that a thin layer of viable tumor tissue remained that was fed by newly formed vessels. The cells supplied by those vessels showed increased expression of a growth factor, as is often found in oxygen-deficient areas.

To disrupt this secondary formation of blood vessels, the researchers blocked the growth factor VEGF by administering an antibody called bevacizumab after the blood vessel-destroying agent OXi4503. The combined approach led to enhanced leukemia regression.

The research, funded by the National Institutes of Health and the Leukemia and Lymphoma Society, has implications for both basic science and clinical research, as the results suggest that potential therapies must be screened against not only leukemia cells, but also the environment with which they interact.

"It's a major paradigm shift," Rafii said.

Describing the studies as "elegant," Judith Karp, M.D., a professor of oncology and medicine and director of the leukemia program of the Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, said the findings support the notion that VEGF and the vascular milieu are extremely important in cancer cell survival, and that targeting them might be a good anti-cancer strategy. Karp pioneered the use of bevacizumab — the antibody used in the UF studies — after chemotherapy, which resulted in remission among patients with cancer that was resistant to chemotherapy or that had returned after treatment.

"The results are extremely exciting and need to be implemented clinically in a very prioritized and timely fashion," said Karp, who was not affiliated with the study.

Indeed, the U.S. Food and Drug Administration quickly gave its approval in April for a phase 1 clinical trial. That means the treatment could be available by late 2010 or the start of 2011 to eligible study volunteers at Shands at UF, as soon as the researchers are able to obtain the necessary funding for the trial.

The initial two-year trial is not designed to determine whether the drug works, but rather to determine the maximum tolerable dose. It will involve three dozen individuals age 18 and older whose cancer is growing despite previous treatment. Trial details are at the National Institutes of Health website http://clinicaltrials.gov. Search for "NCT01085656."

Czerne M. Reid | EurekAlert!
Further information:
http://www.ufl.edu

More articles from Health and Medicine:

nachricht Observing the cell's protein factories during self-assembly
15.06.2018 | Charité - Universitätsmedizin Berlin

nachricht Scientists unravel molecular mechanisms of Parkinson's disease
13.06.2018 | The Francis Crick Institute

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: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

Im Focus: Photoexcited graphene puzzle solved

A boost for graphene-based light detectors

Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...

Im Focus: Water is not the same as water

Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.

From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

A sprinkle of platinum nanoparticles onto graphene makes brain probes more sensitive

15.06.2018 | Materials Sciences

100 % Organic Farming in Bhutan – a Realistic Target?

15.06.2018 | Ecology, The Environment and Conservation

Perovskite-silicon solar cell research collaboration hits 25.2% efficiency

15.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>