The Academy: March 2007

THE ACADEMY

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University of California, San Diego (UCSD) Salk Institute for Biological Studies La Jolla Institute for Allergy and Immunology UCSD Researchers Discover a Protein Linking Inflammation and Cancer

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esearchers from the University of California, San Diego (UCSD), the Salk Institute for Biological Studies, and the La Jolla Institute for Allergy and Immunology reported in the January 26 issue of Cell that they found a mechanism through which chronic inflammation can promote cancer.

The study found that p100, a protein that is related to inflammation, is also an integral part of cellular development. This means that what were once thought of as two distinct cell processes, development and inflammation, actually respond to and are dependent on the other process.

This also explains why chronic inflammation has been linked to cancer. “Although there is plenty of evidence that chronic inflammation can promote cancer, the cause of this relationship is not understood. We have identified a basic cellular mechanism that we think may be linking chronic inflammation and cancer,” said Alexander Hoffmann, PhD, an assistant professor of chemistry and biochemistry at UCSD, who led the study.

What the researchers found was that increases in the concentration of p100 are caused by inflammation; they also found that p100 is necessary for certain steps in normal cell building, which allows it to act as a signal between inflammation and the building process.

“In the case of chronic inflammation, the presence of too much p100 may over-activate the developmental pathway, resulting in cancer,” stated Dr. Hoffmann. This development could lead to new breakthroughs in cancer therapies, since most of the cellular signaling for the development process takes place outside the cell. Finding ways to stop cancer outside the cell could be easier for researchers than getting therapies into the cells.

The research team’s focus was initially drawn to the p100 protein through a mathematical model they developed to run 98 biochemical reactions in both the inflammation and development pathways. The model suggested that significant inflammation would lead to a sustained increase in p100.

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University of Michigan's Comprehensive Cancer Center Stanford University School of Medicine

Biomarker for Head and Neck Stem Cells Discovered

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esearchers believe that CD44, which is a biomarker for breast cancer stem cells, is also a biomarker for lung and neck cancer stem cells. According to a report in the January 16 issue of Proceedings of the National Academy of Science, researchers at the University of Michigan’s Comprehensive Cancer Center and Stanford University School of Medicine have found that CD44 on head and neck tumor cells is indicative of the replicating cancer cells.

Recent data has supported the theory that replicating cancer cells, or cancer stem cells, are the only cells that are essential to cancer’s growth and progression. Cancer stem cells have been found in breast, brain, and colon cancer, and now, in this study, they have been found in head and neck cancer.

The study separated out cancer cells taken from head and neck cancer by their expression of CD44. The divided cells were then implanted into immune-deficient mice to promote tumor growth. The researchers found that the CD44 cells were able to grow new tumors that were identical to the previous tumor, while the non-CD44 cells were unable to produce new tumors. Researchers also found that the new tumors contain cells that both expressed and didn’t express CD44.

“The CD44-positive cells contain the tumorigenic cells, but we don’t think that’s a pure population of cancer stem cells. We still need to drill down further to find the subpopulation of those cells that is the pure version,” states Mark Prince, MD, author of the study, assistant professor of otolaryngology at the University of Michigan Medical School, and section chief of otolaryngology at the VA Ann Arbor Healthcare System.

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University of Rochester

Expression of Cancer Promoter Linked to Body Mass

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recent study found that it isn’t our long lifespan that has, through natural selection, reduced the expression of telomerase, an enzyme that increases the lifespan of cells; it’s our body mass. According to the study conducted by Vera Gorbunova, PhD, assistant professor of biology at the University of Rochester, small rodents’ telomerase expression is related to their body mass. The study was published in Aging Cell.

Previously, it was believed that our bodies suppressed the expression of telomerase because the expression of telomerase with our longer life spans would increase the probability of cell mutations and cancer. For rats, it was believed that they expressed telomerase because the advantages of rapid healing outweighed the probability of developing cancer due to their relatively short lifespan.

The study conducted by Dr. Gorbunova initially compared the lifespan of 15 rodents from around the world with diverse sizes and lifespans; however, she discovered that there was no correlation between their lifespan and their expression of telomerase. It is actually the number of cells that an animal has, rather than the number of years they will live, that has selectively effected expression of telomerase.

Because humans and other animals fully suppress telomerase, the important question for drug researchers is “Do animals with larger body masses have other mechanisms, outside of telomerase suppression, that prevent cancer?” This might lead to a new area of study for possible biological solutions to cancer prevention.

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Yale School of Medicine

Position of Mutations Can Affect the Risk of Cancer

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t has been discovered that gene mutations linked to cancer happen more often than previously thought. According to a study published in the Journal of the National Cancer Institute’s December 6 issue, BRCA1 and BRCA 2 mutations occur in almost 1% of the population and could be responsible for a variety of cancers.

The study examined the presence and rate of BRCA1 and BRCA2 in women who were recently diagnosed with ovarian cancer. The women were also questioned about the incidence of cancer in their parents, siblings, and children. Though elevated BRCA1 and 2 mutations have proven to increase cancer risk, the researchers discovered that certain mutations carry greater or less of a risk for developing cancer.

“We found that cancer risk differed for each gene according to the mutation’s position in the gene,” said lead researcher, Harvey Risch, MD, professor in the division of chronic disease epidemiology in the Department of Epidemiology and Public Health at Yale School of Medicine. “When choosing which individuals to screen for mutations, we should consider all kinds of cancers among family members, not just breast and ovary and not just cancers in females.”

While Dr. Risch’s recent study looked at the rate of BRCA1 and 2 mutations in women with recently diagnosed ovarian cancer, the researchers at Yale School of Medicine plan to follow up this study by examining these mutations, and the risk associated with them, in a study with a larger population.

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University of Illinois at Chicago Improved

Exams Benefit Oral Cancer Patients

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study presented at the “Multidisciplinary Head and Neck Cancer Symposium” in Rancho Mirage, CA, found that more advanced screening processes, which would generate more accurate diagnoses, would improve the survival of patients with early-stage oral cancer.

The researchers from the University of Illinois at Chicago wanted to study the addition of more modernized techniques in detecting suspect areas of the mouth and throat. The researchers added two pieces of equipment to the standard oral cancer examination, visual inspection of the mouth and observations of the patient. The two tools they used in the exam were a Chemiluminescent light (Vizilite) and toludine blue, a pharmaceutical dye.

In the study, the patients were examined visually by the doctor to determine were the suspicious areas where. The suspect areas where then tested using Vizilite, which was found to improve identification of lesions. After that, toludine blue, which was shown to reduce false positives, was used on the spots, which were then biopsied. After this, the results of these exams were compared to the results of standard exams.

“By combining conventional techniques with more modern techniques, we were able to better diagnose and determine the best options for patients with oral cancer. This approach to diagnosing oral cancer may lead to easier identification of serious pathology, significantly lessening the need for unnecessary biopsies without additional risk of false negatives,” stated the lead author, JB Epstein, professor at the University of Illinois at Chicago.