Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson scientists find calcium is key to slowing colorectal cancer growth

11.02.2003


Allowing calcium to get inside colorectal cancer cells may be one way to stop their growth.

Researchers at Jefferson Medical College and the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia knew that the same bacterial toxin that causes traveler’s diarrhea can stem the growth of metastatic colorectal cancer cells. Now, they may have found out how.

The scientists discovered that the toxin appears to open a cellular door, permitting calcium into tumor cells, which in turn somehow slows cell division. The discovery may lead to new methods of treating colorectal cancer, perhaps by combining the toxin with chemotherapy drugs and other agents.



GianMario Pitari, M.D., Ph.D., assistant professor of medicine at Jefferson Medical College of Thomas Jefferson University, Scott Waldman, M.D., Ph.D., Samuel M.V. Hamilton Family Professor of Medicine and director of the Division of Clinical Pharmacology at Jefferson Medical College, and their co-workers report their findings February 10 in the Proceedings of the National Academy of Sciences Online Edition.

Drs. Waldman and Pitari had previously shown that when the toxin, known as ST, hooks up with a receptor, GCC, on the surface of metastatic colorectal cancer cells, metastatic colorectal cancer cell growth slows considerably. Treating the cells with ST didn’t kill them, but rather lengthened the time of the cell growth cycle, slowing the cells’ growth and spread. The current research takes this work one step further, providing one potential mechanism for this growth inhibition.

"Dietary calcium is the mediator of this antiproliferative effect," says Dr. Pitari, who adds that dietary calcium has been believed to have a role in preventing the formation of polyps and cancer in the colon. "Now, we show that one of the mechanisms by which dietary calcium works is through this pathway. The toxin activates the receptor, GCC, causing an opening of a channel and an influx of calcium into the tumor cell. This influx causes a reduction of cancer cell growth. Somehow there is an interaction between the toxin and dietary calcium in blocking the growth of the tumor.

"The mechanism by which this occurs is very specific and a completely new pathway," he says. "No one has linked this pathway to antiproliferation and inhibition of tumor DNA synthesis," he notes.

In the laboratory, Drs. Pitari, Waldman and their co-workers, including internationally renowned electrophysiologist Andre Terzic, M.D., Ph.D. at the Mayo Clinic in Rochester, Minn., discovered that when ST binds to GCC on the cancer cell surface, a molecule called cyclic GMP is produced. Cyclic GMP, in turn, opens up a calcium channel in the cancer cell, permitting calcium to flow in. The calcium then imparts a signal that slows cancer cell division.

Drs. Pitari and Waldman see several implications from these results. "We think you can use the toxin as an intravenous infusion to treat cancer metastases," says Dr. Pitari. "The toxin will not cross the intestinal lumen, meaning there won’t be the side effects of diarrhea. In this case, you could have only the therapeutic effects of the toxin on a metastatic tumor. We think it could be one way to treat patients who had surgery on the primary tumor, to prevent the formation of metastases or to even treat metastases."

Dr. Waldman explains that when the toxin hooks up with the GCC receptor, it causes two events in the intestine: diarrhea and cell growth inhibition, each through a different pathway. One pathway leads to secretion of water and electrolytes. The other leads to calcium entering the cancer cell and blocking DNA synthesis. "We propose blocking the pathway leading to diarrhea and leaving only the positive effect," says Dr. Pitari. "This might provide a great opportunity to treat the cancer locally. It might also work synergistically with other anticancer drugs."

Next, says Dr. Waldman, the scientists plan to create human colorectal cancer models in so-called nude mice, animals without immune systems, to see if ST can inhibit the growth of tumors in animals.

The technology involved in the research has been licensed from Thomas Jefferson University to Targeted Diagnostics and Therapeutics, Inc. (TDT), based in Exton, Pa. TDT has licensed the rights for the development of therapeutics from the work to Millennium Pharmaceuticals, Inc. in Boston.


###
Contact: Steve Benowitz or Phyllis Fisher
215-955-6300
After Hours: 215-955-6060
E-Mail: steven.benowitz@mail.tju.edu


Steve Benowitz | EurekAlert!
Further information:
http://www.tju.edu/

More articles from Health and Medicine:

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

nachricht Flexible sensors can detect movement in GI tract
11.10.2017 | Massachusetts Institute of 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: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

Im Focus: New nanomaterial can extract hydrogen fuel from seawater

Hybrid material converts more sunlight and can weather seawater's harsh conditions

It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...

Im Focus: Small collisions make big impact on Mercury's thin atmosphere

Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.

Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

Conference Week RRR2017 on Renewable Resources from Wet and Rewetted Peatlands

28.09.2017 | Event News

 
Latest News

A single photon reveals quantum entanglement of 16 million atoms

16.10.2017 | Physics and Astronomy

The melting ice makes the sea around Greenland less saline

16.10.2017 | Earth Sciences

On the generation of solar spicules and Alfvenic waves

16.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>