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 Nanoparticles as a Solution against Antibiotic Resistance?
15.12.2017 | Friedrich-Schiller-Universität Jena

nachricht Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University

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: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>