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 On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

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: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>