When Doctors Make Mistakes

By now, just about everyone is aware of the relationship of COX-2 with arthritis since several companies are constantly advertising their COX-2 medications. You will more than likely recognize Celebrex and Vioxx as the most visible. What you are much less likely to realize is that COX-2, which converts arachidonic acid into prostaglandins in rheumatoid arthritis, also increases in its amount in cancer cells where it triggers the production of prostaglandins. This is because the gene for COX-2 is turned on very early in cancer. Once prostaglandins are involved, they bind to tumor cells and turn on other genes. These genes assist in generation of new blood vessels, helping feed the rapid growth of the tumor cells.

Researchers want to know whether interfering with the COX-2 gene might prove to be an effective way to treat cancer. Many studies are in progress, including one reported by a team from Washington School of Medicine in St. Louis. Led by Shrikant Anant, this group found that a protein called cytidine uridine guanosine protein-2 (CUGB2) is capable of destroying several types of cancer cells. In their article called "Coupled mRNA Stabilization and Translational Silencing of Cyclooxygenase-2 by a Novel RNA Binding Protein, CUGBP2," which they published in the journal Molecular Cell, Anant's team inserted the CUGBP2 into cultured tumor cells. The result was that more than 70% of these cells self-destructed. That's pretty encouraging!

Putting things together, the progression of changes involved is thought to proceed due to interference with strict regulation of important proteins. In a cell's life, replication and division take place in a normal cycle. First, RNA is made. Then the RNA is translated into proteins, which must be made at precisely the right time if the cycle is to work properly. This tight regulation is believed to be critical. Even a few minutes of interference can result in serious alterations in the cell leading to changes such as cancer. The timing is tightly controlled by the activity of messenger RNA. Anant's group found that the interaction between CUGBP2 with the mRNA for COX-2 was disturbed in eight types of human cancer cells. All of them had very low levels of CUGBP2. When the gene responsible for production of CUGBP2 is turned down this protein decreases. The result is that cancer can now grow much easier, having better vascularity. They also found that cancer cells could no longer make COX-2 when CUGBP2 attaches to COX-2 mRNA. This causes the cancer cells to die. CUGBP2 may be acting as one type of master switch that the cell uses to control other key proteins according to one of the authors, Dieckgraefe.

Another important finding was that CUGBP2 isn't toxic to healthy cells, and when introduced into cancer cells at levels found in normal cells, the cancer cells died. This may lead to a new way to kill tumors without harming normal tissues. Perhaps it can be used as an adjunctive therapy, as well, assisting other modalities to become more effective.

A good general wins battles because he possesses better well-trained soldiers, better equipment, etc., but a major key to his success is precise knowledge of the manner in which the enemy operates and is supplied. This is just as true when fighting disease as it is for fighting wars. As we learn more and more about the complex inner workings of cancer cells, and their vascular supply lines, we become more adept at finding ways to destroy them. The sort of research undertaken by this team is essential if we are to conquer this dread menace without harming normal tissues.

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Cartoons and Poems following each article are created and copyrighted by Dr. Ackerman and cannot be copied or reproduced without his permission. Copyright © 2006 by Marvin Ackerman, M.D.

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