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Pathology

Houston, Texas

Ayala-Wheeler Lab
Pathology
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Articles and Press Releases

Technology puts Baylor cancer research on the fast-track HOUSTON
By John Tyler, Baylor Press
(Nov. 1, 2002) - If scientists' traditional method for studying tissue under a microscope could be compared to a slow-cook oven, Baylor College of Medicine cancer researchers have pulled out the microwave. Research that could someday result in cures or new therapies for patients suffering from various forms of cancer is speeding forward using unique arrays of tissue samples, a specialized microscope and a computer database. Researchers are able to simultaneously study slides with an array of tissue samples from hundreds of prostate and breast cancer patients, quickly and conveniently. It's these differences between patient tissue samples that can help researchers answer puzzling biological questions or to find a biomarker's ability to predict an outcome. With the large numbers of patients' tissue samples, scientists have statistical power. "We didn't have that before," said Dr. Gustavo Ayala, associate professor of pathology. "The reason we haven't had biomarkers for clinical use is that the data we have been producing has been biased, with insufficient power, and without validity when looking at groups of individuals." Ayala said Baylor has gathered 15 years of tissue samples and follow-up data for as many as 4,000 prostate cancer patients, making it one of the most immense prostate tissue banks anywhere. Baylor's Breast Center also has an extensive collection of tissue samples for its studies. Tissue micro-array technology allows scientists to construct slides with rows of small tissue samples from numerous samples. With the aid of a computer, Baylor researchers are able to quickly examine numerous samples to find similar characteristics - or biomarkers - within sets of tumors from large numbers of patients. The college's Breast Center also uses the technology to study breast cancer biomarkers. "If you wanted to study 890 patients before this technology existed you'd have to study 890 slides," he said. "Being able to look at that many patients assures you can quickly measure smaller and smaller differences."
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Baylor study finds prostate cancer cells are fed by nerves
By John Tyler, Baylor Press
HOUSTON -- (May 22, 2002) -- A recent Baylor College of Medicine study indicates that prostate cancer spreads by attaching to nerves because they feed the cancerous cells, not because it is the path of least resistance outside the gland, as once thought. According to Dr. Gustavo Ayala, assistant professor of pathology, if prostate cancer remains in the prostate, it is less likely to develop further. It only progresses when it leaves the gland, and in 80 percent of cases it does that by wrapping around nerves. Researchers found that about 15 genes were increased over threefold in the cancer cells wrapped around the nerve as compared to the cancer cells away from the nerve. The genes involved were mostly regulators of cell death. "This is an interactive relationship because the nerve is providing the cancer the fuel to keep growing," Ayala said. "Understanding these specific mechanisms of this cancer-nerve interaction is key to developing therapies." If cancer growth can be slowed down, then less aggressive cancers will be treated with fewer deaths, and treatment for faster spreading cancers would finally be obtainable, he said.

Ayala and his co-investigator, Dr. Thomas Wheeler, professor of pathology, found that placing a nerve from a mouse in a petri dish with prostate cancer cells caused both to grow. Additionally, the nerve grew toward the cancer cell colony, indicating the nerves and cancer cells were feeding each other. For more than three decades, scientists have believed cancer cells were wrapping around nerves and traveling through them because it was the path of least resistance through the prostate's thick, fibrous covering.
- John Tyler
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The nerve and prostate cancer - a symbiotic relationship
By Ruth SoRelle, MPH (original article)

It's no secret that prostate cancer wraps around nerves. The process was first identified 100 years ago. What it means, though, could have important implications in the treatment of spreading prostate cancer in coming years.

Now Gustavo Ayala , MD , associate professor of pathology and his colleagues at Baylor College of Medicine in Houston are well on the road to finding out why this phenomenon occurs, what it means to patients and determining how to block it.

Perhaps it began when Thomas Wheeler, MD, BCM professor of pathology determined that the amount of tumor encasing the nerve in prostate cancer was in direct proportion to its virulence. In other words, the more cancer wrapped around the nerve, the worse the prognosis for the patient.

"It really is a very important predictor," said Ayala. "Not only for prostate cancer, but it also works for pancreatic cancer and cancers of the head and neck. These are neurotrophic cancers. They like to invade the nervous system."

Building on that in the laboratory, Ayala established a laboratory model of prostate cancer invading the nerves. What he found was surprising.

"The tumor grew more in the presence of the nerve, and the nerve grew more in the presence of the cancer," he said.

"The big question is 'why does this happen?'" he said. The answer lies in the biological programming of the cells. Like humans, all cells must die. They are programmed to die in a certain space of time - a process called programmed cell death or apoptosis. Life is short for the cells in the skin, which slough off daily. Nerve cells are a different story. They are programmed to live as long as the organism itself.

"The nerve cells have to shut down the mechanisms of apoptosis," said Ayala. "When the cancer starts wrapping around the nerve, it begins feeding off the mechanisms the nerve uses to avoid death. The cancer becomes a parasite of the nerve."

This enables the cancer to shut down its own apoptotic mechanisms and to reproduce prolifically.

Using a special technique called a cDNA array, he found 15 genes that were upregulated (especially active) in this activity. One he has studied is called nuclear factor kappa B or NF ? B. When this gene goes to the nucleus, it becomes a transcription factor - a component of the mechanism that translates the genetic information in a gene into a protein.

In studies of tissues from 250 patients with prostate cancer, Ayala and his colleagues have found that when NF ? B acts strongly in the nucleus of the cells, the patient is more likely to have the prostate cancer return and return sooner. He and his colleagues analyzed only the cancer directly around the nerve.

"That's significant," said Ayala. "Only when the gene goes to nucleus do you have a worse prognosis."

The next question was how does the cancer get around the nerve? Ayala said he has a candidate gene that may answer that question. The normal function of the gene has nothing to do with the prostate, but tests are promising, he said.
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