Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Duke Scientists Identify New Way To Block Blood Vessels That Feed Cancer Growth

21.05.2004


Scientists from Duke University Medical Center have identified the "master switch" that cancer cells use to dispatch protective messages to nearby blood vessels, fortifying the vessels against deadly onslaughts of radiation.



The messages enable blood vessels to survive and ultimately nourish any remaining cancer cells that escape toxic radiation therapy.

Radiation biologists from the Duke Comprehensive Cancer Center identified the master switch as a protein called "Hypoxia Inducible Factor" (HIF-1) that turns on production of these protective messages.


They suppressed HIF-1 with experimental drugs given together with radiation therapy in animals with cancer. In doing so, they successfully inhibited blood vessel growth in tumors and, thereby, the growth of tumors themselves.

The Duke scientists hope to test this potential new therapy plus radiation in humans within the very near future. Results of their current findings are reported in the May, 2004, issue of Cancer Cell.

"HIF-1 is the switch inside cancer cells that gets turned on by radiation therapy," said Mark Dewhirst, Ph.D., DVM, professor of radiation oncology at Duke and principal investigator of the study. "Once it is activated, HIF-1 then triggers the production of well-known growth factors such as VEGF and bFGF, as well as more than forty different protein signals that regulate tumor metabolism, metastasis and angiogenesis." Angiogenesis is the process by which cancer cells grow new blood vessels to nourish and sustain themselves.

"By blocking the master switch, we effectively blocked many of the proteins which promote angiogenesis," said Dewhirst.

The Duke discovery follows dozens of recent developments in the field of anti-angiogenesis, in which scientists have attempted to block specific proteins that give rise to or protect tumor-feeding blood vessels.

The most noteworthy success has been Avastin, the first drug to be approved by the FDA to suppress angiogenesis in patients with spreading colorectal cancer. Avastin inhibits the protein VEGF and has been shown to extend patients’ lives when taken together with chemotherapy.

Dewhirst and first author Benjamin Moeller said their technique of suppressing HIF-1 expression could, theoretically, be a more potent inhibitor of blood vessel survival than the current approach of just suppressing a single protein, such as VEGF.

"We’re employing a treatment strategy where we accomplish two hits -- killing the cancer cells with radiation and blocking their blood vessel survival with an anti-HIF drug," said Moeller, a graduate student in the Duke M.D./Ph.D. program. "By pinpointing and blocking the source of all the signals, we have successfully halted the cancerous blood vessel growth in animals without harming normal blood vessels."

Approximately half of all cancer patients in the U.S. are treated with radiation therapy. However, the success of therapy depends largely on how sensitive a tumor’s blood vessels are to radiation. If blood vessels in the tumor survive after radiation, they can provide nutrients to the surviving cancer cells to begin rebuilding the tumor.

Thus, knowing how HIF-1 works inside cancer cells is critical to manipulating its behavior and making its blood vessels more responsive to radiation, said Moeller.

It is already known that radiation boosts oxygen levels inside cancer cells. In the new study, Moeller demonstrated that the infusion of oxygen releases pent-up RNA, the genetic blueprint molecule, for HIF-1 protein which is bound up in tiny particles called stress granules. The oxygen disintegrates these stress granules and allows HIF-1 to be produced and to engage in production of growth factors.

Secondarily, the infusion of oxygen produces "reactive oxygen species" -- also known as oxygen free radicals -- inside cancer cells. Reactive oxygen species were also shown to boost HIF-1 production, the study showed.

"Tumors so desperately seek to protect themselves against radiation that they have two completely different mechanisms for boosting HIF-1 regulated gene production to protect their blood vessels," said Dewhirst. The team’s unexpected findings shift the accepted paradigm of how HIF-1 works inside cancer cells and provides major insight into how HIF-1 regulates angiogenesis after radiation therapy, he said.

"We’ve known that oxygen levels and blood vessel growth inside tumors are two major influences on how a tumor responds to radiation and chemotherapy," said Dewhirst. "Now we’ve shown for the first time that HIF-1 is a major target we could block in combination with radiation therapy or any other therapies that causes oxygen levels to rise after treatment."

Becky Levine | dukemed news
Further information:
http://dukemednews.org/news/article.php?id=7618

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

'Lipid asymmetry' plays key role in activating immune cells

20.02.2018 | Life Sciences

MRI technique differentiates benign breast lesions from malignancies

20.02.2018 | Medical Engineering

Major discovery in controlling quantum states of single atoms

20.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>