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Cancer is losing blood

A new method to inhibit the spread of malignant tumors

By Marit Selvin

Isaiah Fiedler, director of the Advanced Cancer Research Institute at the University of Texas - one of the three most important cancer centers in the US - and one of the leaders in this field, is currently in Israel. Fiedler, an Israeli born in Jerusalem, came to Israel to help the Cancer Society in the "Knock on the Door" operation. These days he is also conducting innovative experiments on humans, which are concerned with the biological cure of cancer.

The treatment of cancer is extremely complex: in most cases the tumor spreads in the body even before it is discovered; Cancer cells that are formed while constantly dividing are resistant to treatments due to genetic changes they undergo during division; Cancer of the same type varies from patient to patient, and in the patient himself, the metastases are different from each other.

In view of this, Fiedler decided to try to find a common denominator for the simplified cancer. In this way, he believed, it would be possible to find a treatment that would suit a large number of tumors. "What characterizes all body cells, including cancer cells, is their need for oxygen. The oxygen circulates to the tissues from the blood capillaries, and to receive oxygen supply
The tissue cells must be in close proximity to the capillaries. If they stray from the blood capillaries more than a tenth of a millimeter, they are doomed to die. Therefore, when a cancerous tumor begins to divide and grow, it affects the formation of blood vessels around it," says Fiedler.

Indeed, the cancer cells secrete special substances, which accelerate the division of endothelial cells - the cells that build the blood capillaries. It turns out that the tumor secretes the same substances that the normal body cells secrete, for example in the case of an injury, when it is necessary to restore the blood capillaries. However, when the situation is corrected this process ends, while in cancer it continues without a break. The process of creating new blood vessels in normal conditions is regulated through a balance between substances that accelerate the division of endothelial cells, and substances that inhibit their division.

"I asked myself," says Fiedler, "whether the excessive division of the endothelial cells in the blood capillaries in the tumor is caused by an excess of catalytic substances or by a lack of inhibitory substances. I decided to concentrate on finding the brake."
Fiedler discovered that a protein called interferon - known as the one that protects the body's cells from viruses that penetrate it - is the one that acts as a brake on the process of creating new blood vessels. In experiments he conducted on mice, he found that the interferon suppresses the formation of new blood vessels by blocking the genes that produce the substances that accelerate the division of endothelial cells.

"A week after our results were published, I heard at a conference a lecture by Prof. Yehuda Folkman (the man who brought about the breakthrough in cancer treatment by blocking the blood supply to the tumor), about the rapid healing of blood capillary cancer (hemangioma) using small amounts of interferon. Volkman didn't understand how and why this was happening, but I already knew, and then we started a joint study that showed that the cancer cells did indeed stop producing interferon."

During the many genetic changes that cancer cells undergo, they lose the gene that produces interferon, and therefore they are unable to inhibit the formation of new blood vessels, something that serves the interests of the tumor well - to keep dividing continuously. Fiedler found that the gene that codes for interferon is found on chromosome 9, and that it is missing in certain cancerous tumors such as bladder cancer, skin cancer, gastrointestinal cancer and lung cancer.

The next question was, of course, whether it is possible to use interferon to cure cancer. Fiedler began injecting interferon into animals and encountered an interesting phenomenon: small amounts of interferon did not help, nor did large amounts, and only an intermediate amount helped to inhibit the genes responsible for creating new blood vessels. "I didn't publish the results for a year and a half because I couldn't explain why a large amount of interferon had no effect," says Fiedler. "A few months ago I found the explanation."

Interferon in large quantities, it turned out, is toxic to the body. Therefore, the body "needs a biological mechanism that will stop its action in time", says Fiedler. Indeed, he found that a large amount of interferon causes the formation of a protein that prevents the interferon from working; The protein neutralizes the receptor to which the interferon binds.

The discovery sheds new light on the biological cure of cancer. "The body has learned to defend itself against the toxicity involved in large quantities of biological substances. Therefore, there is no meaning to high doses of biological material, and in my humble opinion, there is no need for a quick cure either," says Fiedler.
"We may have to treat cancer after the containment phase as a chronic disease." One of the options is daily treatment with interferon. Fiedler is now trying treatments in humans at different doses to find the optimal one. The experiments are not over yet and according to him it is still too early to talk about results.

"The interferon treatment will not be the ultimate treatment," says Fidler, "it will be combined with the conventional treatments, but what excites me about the whole story is that a substance that has a physiological function in the body could possibly return the cancer to a physiological function, where it will not threaten our lives."
{Appeared in Haaretz newspaper, 1/11/2000{

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