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Luminescent compounds for the detection of cancerous tumors

A series of innovative imaging materials will be able to illuminate tumors at the very beginning of their development - before they become malignant - and thereby signal their development into more aggressive cancerous tumors.

Prof. Lawrence Marnett, right, and his colleagues, Prof. Jashim Uddin, right, Prof. David Piston and Brenda Crews, research a compound that causes tumors to glow. Photography: Joe Howell
Prof. Lawrence Marnett, right, and his colleagues, Prof. Jashim Uddin, right, Prof. David Piston and Brenda Crews, research a compound that causes tumors to glow. Photography: Joe Howell
The compounds - luminous inhibitors of the enzyme cyclooxygenase-2 (cyclooxygenase-2, COX-2) - could have a variety of applications for identifying early tumors, monitoring the development of the tumor from benign to malignant, and determining the tumor's borders during surgical removal.

"We are extremely excited about these innovative materials and are moving towards their development to the stage of human medical trials," said Lawrence Marnett, head of the team of scientists from Vanderbilt University (Nashville, Tennessee, USA) who developed the compounds, and which were published in the scientific journal Cancer Research.

The COX-2 enzyme (Wikipedia entry) is a desirable biological component for molecular imaging. The enzyme does not appear in most healthy tissues, and is "activated" only in inflammatory wounds and tumors, explains the lead researcher.

"The enzyme works in the early stages of pre-malignancy - in pre-malignant tumors, but not in the healthy tissues surrounding them - and as the tumor develops and becomes more and more malignant, the concentration of the enzyme rises and rises," explains the researcher. Compounds that bind selectively to the enzyme - and which are attached to a luminescent marker - will be able to function as a beacon (radiant point) for locating malignant cells and inflammatory areas.

This team of researchers had previously demonstrated that luminescent inhibitors of this enzyme - called fluorocoxibs - could be used as effective detectors for protein binding, but they were not suitable for cellular or in vivo imaging. "It was a serious challenge to prepare a compound that is both selective towards COX-2 (and does not bind to the close enzyme COX-1), also has desirable protective properties and is able to penetrate the tissues of the living body," explains the researcher.

In order to prepare such compounds, the research team started from the skeleton of the chemical structure of two anti-inflammatory drugs: indomethacin (The entry in Wikipedia) and celecoxib (The entry in Wikipedia). Next, they attached a variety of luminescent chemical groups to the skeleton of the structure, eventually synthesizing a series of about two hundred different compounds. The team next examined each of the compounds to determine how they interact with the COX-2 and COX-1 enzymes in terms of their selectivity and their ability to glow in cultured cells and in the living body. Only two compounds "reached the final".

Using familiar models, the researchers tested the activity of these two compounds. In all the cases tested, both compounds accumulated only in the malignant or inflamed tissues, and they were also able to glow in the cells. In order to advance the use of the materials for human medical trials, the team will conduct additional toxicology and pharmacology tests in the next phase, as well as develop the tools for the finished test kits.

"Since COX-2 enzyme levels increase during the development of cancer, in almost all solid tumors, we believe that this imaging tool has many and varied applications."
The materials could also be used for the directed and selective transfer of chemotherapy drugs directly to the malignant cells, which have high levels of the enzyme, by replacing the luminescent marker with an anticancer drug.

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2 תגובות

  1. Eyal,
    You shouldn't explode. Cancer is a general name for many diseases that have a common feature of disrupting the normal development of certain cells in different body organs. Therefore there are also many revelations. There are also many successes, there are cures for some diseases and some of the diseases called cancer become chronic that you can live with.

  2. Still no one responded.. hmm..
    Of all the sensational discoveries in the field of cancer, there is a feeling that since the disease should have been just another disease with a cure. Or at least in the near future.
    Each time a different discovery or rather a different method for the targeted elimination of a cancerous tumor. You can be blown away by this - how many different revelations and how different they are. It seems as if each research group works alone and is the only one in its field. Obviously it's not like that, but that's the feeling you get after all these articles.

    For example, the current article - gives the feeling that the ultimate solution to cancer, in its various forms, is just a moment at hand. But it is clear that this will not be the solution just because of the "wolf wolf!" 

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