Navigation Links
IBM Transforms the Art of Scientific Expeditions

Scientists have shown they can dramatically enhance radiation's cancer-killing effects by blocking a "master switch" in cancer cells that promotes cancer growth. Blocking a protein called HIF-1 after radiation therapy doubled the length of time it took for human cancers to begin growing again in mice, said the radiation biologists from the Duke Comprehensive Cancer Center.

Each therapy alone had limited or no benefit on the tumor, because tumors are skilled at circumventing individual therapies and finding new ways to grow. But together, the two therapies more potently inhibited a tumor's ability to sustain and nourish itself by growing new blood vessels around the tumor.

Most importantly, the scientists clarified how this master switch, Hypoxia Inducible Factor or HIF-1, promotes a cancer cell's ability to grow, nourish, energize and develop blood vessels that support its growth.
The answers they yielded are complex, yet promising, for the future treatment of cancer patients, said Mark Dewhirst, Ph.D., DVM, professor of radiation oncology at Duke.

Results of the research, led by Dewhirst and conducted by M.D./Ph.D. candidate Ben Moeller, will be published in the August 15, 2005, issue of Cancer Cell.

"We've shown that blocking HIF-1 at the wrong time therapeutically in a cancer cell yields no benefit and can actually impede other cancer treatments," said Dewhirst. "But when we block HIF-1 at the appropriate time, it substantially increases a tumor's response to radiation therapy."

Specifically, they found that blocking HIF-1 immediately after radiation prevented new blood vessels from developing and nourishing cancer cells that survived radiation. Two days after tumors were irradiated, there was almost no detectable vasculature ?blood vessels feeding the tumor.

"We've employed a treatment strategy where we accomplish two hits ?killing the cancer cells with radiation and then blocking their blood vessel survival a nd re-growth by inhibiting HIF-1," said Moeller.

Conversely, when the scientists blocked HIF-1 before radiation, there was no overall inhibition of tumor growth. The tumor's center became "necrotic" or populated with dead cells, but the perimeter of the tumor continued to grow.

In fact, blocking HIF-1 before radiation was detrimental to radiation's effects: it prevented cancer cells from engaging in the very behaviors that radiation targets for destruction, said Dewhirst.

"HIF-1 assists cancer cells in dying by a process of self-directed suicide called 'apoptosis,'" said Dewhirst. "If HIF-1 is inhibited prior to radiation, it will make the cell less sensitive to apoptosis and will thereby make the tumor cells more resistant to radiation."

Moreover, because radiation itself boosts HIF-1 levels, blocking HIF-1 at the height of its activity ?after radiation has occurred -- is the most logical sequence of therapy, said Dewhirst.

HIF-1 has become the focus of numerous anti-cancer therapies worldwide, said Dewhirst. Yet its impact on cancer cells is so diverse ?it regulates more than 70 genes -- that simply blocking its activity without regard to its myriad effects has yielded conflicting results. Some of HIF-1's effects promote cancer, while others inhibit cancer, so it is critical to block the protein at a juncture where it promotes cancer growth.

The environment inside the tumor ?and the timing of a given treatment -- can make all the difference in a tumor's response to that therapy, said Moeller.

"Just as putting on a coat and gloves in the middle of summer would yield no benefit and could actually cause harm, blocking HIF-1 at the wrong time and place produces no benefit," said Moeller. "But blocking HIF-1 in the right environment can dramatically inhibit the growth of new blood vessels that feed the tumor."

A multitude of factors influence how HIF-1 behaves in a cancer cell. Cells that are low in oxygen or "hypoxic" do not respond as well to radiation and chemotherapy. Blocking HIF-1 production does not increase oxygen levels, but it does alter the behaviors that are caused by hypoxia.

Similarly, tumors with an intact tumor suppressor gene known as p53 respond more readily to radiation and to HIF-1 inhibition than tumors with a mutated P53 gene. Understanding such factors can aid scientists in determining the best conditions under which to inhibit HIF-1.
"We want to maximize the benefits of HIF-1 blockage while minimizing the drawbacks," said Moeller.

Moeller used a unique, targeted approach of blocking HIF-1 in cells to ensure that HIF-1, and not other proteins, was responsible for the effects they saw. He inserted a mutated form of HIF-1 into the cancer cell and turned it on and off by exposing it to the antibiotic tetracycline.

With this reversible switch, the team could observe the effects while HIF-1 was active and when it was blocked. Drugs to block HIF-1 have been used in previous studies conducted at Duke and elsewhere, but such drugs inhibit other proteins as well, making it impossible to distinguish which effects are related to HIF-1 and which are not.

The team's next step is to test the effects of blocking HIF-1 following chemotherapy. The research was funded by the National Cancer Institute, the Howard Hughes Medical Institute and the Aeolus Corporation.


'"/>

Source:


Related biology news :

1. Software Tool for Converting Scientific Text into a Database of Functional Relationships
2. Scientific issues associated with carbon-neutral energy sources such as cellulosic ethanol
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/4/2017)... --  EyeLock LLC , a leader of iris-based identity ... and Trademark Office (USPTO) has issued U.S. Patent No. ... iris image with a face image acquired in sequence ... th issued patent. "The issuance ... multi-modal biometric capabilities that have recently come to market ...
(Date:3/30/2017)... -- The research team of The Hong Kong Polytechnic ... by adopting ground breaking 3D fingerprint minutiae recovery and matching technology, ... accuracy for use in identification, crime investigation, immigration control, security of ... ... A research team led by Dr ...
(Date:3/28/2017)... 2017 The report "Video Surveillance ... Servers, Storage Devices), Software (Video Analytics, VMS), and Service ... Forecast to 2022", published by MarketsandMarkets, the market was ... projected to reach USD 75.64 Billion by 2022, at ... base year considered for the study is 2016 and ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... Md. (PRWEB) , ... October 11, 2017 , ... ... digital pathology, announced today it will be hosting a Webinar titled, “Pathology is ... Advanced Pathology Associates , on digital pathology adoption best practices and how Proscia ...
(Date:10/11/2017)... ... October 11, 2017 , ... A new study ... in frozen and fresh in vitro fertilization (IVF) transfer cycles. The ... IVF success. , After comparing the results from the fresh and frozen transfer ...
(Date:10/10/2017)... , ... October 10, 2017 , ... ... Center’s FirstHand program has won a US2020 STEM Mentoring Award. Representatives of the ... for Excellence in Volunteer Experience from US2020. , US2020’s mission is to change ...
(Date:10/10/2017)... ... October 10, 2017 , ... ... process optimization firm for the life sciences and healthcare industries, announces a presentation ... San Francisco. , The presentation, “Automating GxP Validation for Agile Cloud Platforms,” will ...
Breaking Biology Technology: