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February
24, 2003 Mary Ann (M.D., Ph.D.) and Donald (Ph.D.) Sens, a husband-and-wife research team at the University of North Dakota School of Medicine and Health Sciences, say that when some types of cancer cells overproduce a specific protein, the information can be used to determine the cancer's stage of development and how aggressively to treat it. The Sens' two cancer research projects - both funded by the National Institutes of Health (NIH) - relate to a protein called metallothionein (pronounced met-aloe-THIGH-oh-neen). Normally, cells produce metallothionein to protect themselves from cadmium, a toxic heavy metal. In their research, the Sens have found that metallothionein is overexpressed in some human cancers.
In their search for cancer-related biomarkers, the Sens rely on excess diagnostic human tissue samples that have been discarded as medical waste. Using these samples, they have developed models of tumor cell lines, enabling them to bypass animal testing. "This is called retrospective research because we're looking at samples from pre-existing specimens," says Mary Ann, a pathologist and chair of the Department of Pathology at the UND medical school. "When we test a new biomarker for prostate cancer, we need to determine if it can predict what will happen. "I look at the tissue sample under a microscope to see if it has a certain protein. If it does, I ask whether it makes a difference. I already have the answer because I'm looking at a sample from 20 years ago and I know what happened to the patient." The Sens' research could influence the decisions doctors make about how cancers are treated today. "With the information biomarkers provide, we can say, yes, this is a bad cancer or, no, this cancer is not going to progress," Donald explains. "We also know that when metallothionein is overexpressed, it interferes with Cisplatin, a chemotherapy drug used to treat cancer patients." In addition to research on using biomarkers as a diagnostic tool, the Sens have a second NIH grant to study the cause of metallothionein overexpression in the kidneys and what happens when it occurs. "We use our tissue culture models in the lab to manipulate genes and discover how a biomarker really works," says Donald. "We take the metallothionein gene, put it in a cell that doesn't normally have it and see what happens. "We're attempting to prove that it starts binding up all the extra zinc in the cell because zinc is very similar to cadmium. But to live, you need zinc as a mineral," he says. "When metallothionein takes zinc from many other proteins that need it, the cell loses its proper mechanism for growth control." Some of the Sens' work on the metallothionein protein as a biomarker has been published in the American Journal of Pathology (Metallothionein Isoform 3 Overexpression Is Associated with Breast Cancers Having a Poor Prognosis - July 2001) and Environmental Health Perspectives (Metallothionein Isoform 3 as a Potential Biomarker for Human Bladder Cancer - March 2000). Mary Ann Sens became the chair of the medical school's pathology department last August. She and Donald came from the University of West Virginia, bringing with them a research team that includes assistant professors Scott Garrett, Ph.D., and Seema Somji, Ph.D., and graduate students Volkan Gurel and Seongmi Park, as well as two, $1.2 million NIH research grants, each for four years. H. David Wilson, M.D., vice president for health affairs and dean of the medical school at UND, says bringing in the Sens and their research team transforms a department that was traditionally focused on education to one engaged in both education and research. Helping to make it possible was start-up funding for new faculty from the North Dakota Biomedical Research Infrastructure Network (BRIN) through the state's Experimental Program to Stimulate Competitive Research (EPSCoR). "The start-up package, including the funding from BRIN, was very helpful," says Wilson. "Our commitment to the Sens includes whatever they need from the medical school standpoint, plus the assistance from BRIN and EPSCoR. Putting all of our funding dollars together obviously made us very competitive." Donald Sens says, "We had two young people in our laboratory who were extremely good and this was an opportunity to bring them along. North Dakota wanting to develop research was a unique opportunity to move the program without disrupting it." "With Mary Ann and Donald Sens, we have high quality people who are going to be here for the long haul. Suddenly, we're thought about on the national map," says Wilson. Download
high-resolution photos to accompany this news release. Contact information:
Donald Sens, professor, UND School of Medicine and Health Sciences Department of Surgery, at (701) 777-2561 or dsens@medicine.nodak.edu H. David Wilson, dean, UND School of Medicine and Health Sciences, at (701) 777-2514 or hdwilson@medicine.nodak.edu John Shabb, North Dakota BRIN director, at (701) 777-4946 or jshabb@medicine.nodak.edu
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