Archive for February, 2008

February 2008 Special Report – UNMC researchers: Estrogen derivative may initiate certain cancers

by Vicky Cerino, UNMC public affairs
UNMC researchers are part of a team that studied simple urine samples and found that certain estrogen derivatives can react with DNA to cause damage that may initiate breast, prostate and other cancers.


These findings — which are published in the Dec. 20 issue of the International Journal of Cancer — could result in better assessment of cancer risk and prevention, the researchers said. The team published similar findings in the journal The Prostate in 2006.


“We have a novel approach to cancer. We know the initiating step,” said Ercole Cavalieri, D.Sc., a professor at the UNMC Eppley Cancer Center. “We think prevention of cancer can be solved by eliminating this initiating step.”


The team’s findings were confirmed in a second, larger study and presented at a recent gathering of international scientists and physicians in San Antonio.


The study involves researchers at UNMC, Mayo Clinic and the Italian National Cancer Institute. The majority of the study was funded by a U.S. Army Breast Cancer Research Program Center of Excellence Award.


Estrogens can initiate cancer when natural mechanisms of protection do not work properly in the body, allowing estrogen metabolites to react with DNA.


“If these protections are insufficient, due to genetic, lifestyle or environmental influences, we think cancer can result,” Dr. Cavalieri said. “Now that we have the basic knowledge about this unifying mechanism of cancer initiation, we have a greater sense of urgency to assess people at risk and, at the same time, begin studies of prevention by using specific natural compounds.”


The screening test developed by the researchers analyzes estrogen metabolite profiles in humans and can simultaneously associate the profile with one’s risk of getting breast cancer. It involves testing a one-ounce sample of urine using a sophisticated method called tandem mass spectrometry, which analyzes about 40 estrogen-related compounds, including estrogen-DNA adducts formed by a chemical reaction of estrogen metabolites and DNA.


“We know the initiating step. We think prevention of cancer can be solved by eliminating this initiating step.”
Ercole Cavalieri, D.Sc.

Researchers analyzed estrogen-DNA adducts from 46 women with normal risk for breast cancer, 12 women at high risk of developing breast cancer, and 17 women diagnosed with breast cancer.


They found women at high risk of breast cancer and the women with breast cancer had significantly higher levels of the estrogen-DNA adducts in their urine samples, while the women with normal risk for breast cancer had low levels of the DNA adducts in their urine.


Nilesh Gaikwad, Ph.D., a UNMC researcher who developed the methodology for the screening tool, said the simple, non-invasive test could easily be applied in the clinical setting.


“We have found the first step that starts a cell down the road to becoming a cancer cell,” said UNMC research collaborator Eleanor Rogan, Ph.D. “By preventing this first step from happening, we think we can stop the development of breast or prostate cancer. The combination of an early detection test for cancer risk with administration of preventing agents should enable us to significantly reduce the number of women and men that develop breast or prostate cancer.”


The results are exciting because they show women at high risk of breast cancer can be identified by the level of adducts in a urine sample, researchers said.


“Similarly, initial studies in men have shown that healthy men have relatively low levels of estrogen-DNA adducts in their urine samples, but men with prostate cancer have much higher levels of the estrogen-DNA adducts in their samples,” Dr. Cavalieri said.


Researchers can use these estrogen-DNA adducts as a measure of cancer risk, he said.


“In addition,” Dr. Cavalieri said, “we have begun to establish how effective natural compounds may be at preventing cancer by determining their ability to reduce the levels of these adducts in urine.”


Dr. Cavalieri also said accumulating evidence suggests that specific metabolites of estrogens, if abundantly formed, can become cancer-initiating agents by reacting with DNA and generating mutations leading to cancer.


DNA is composed of four bases called adenine, guanine, cytosine and thymine.


He said estrogen metabolites react predominantly with the first two DNA bases, adenine and guanine, to form estrogen-DNA adducts.


The resulting damage generated by the reaction can give rise to mutations that eventually initiate cancer. The important estrogen-DNA adducts spontaneously fall out of the DNA, leaving behind gaps that generate the cancer-initiating mutations.
The estrogen-DNA adducts eventually make their way out of cells and are excreted in urine.


“This finding identifies a new biomarker in the urine, which appears to correlate with a women’s risk of developing breast cancer,” said Kenneth Cowan, M.D., Ph.D., director of the UNMC Eppley Cancer Center. “While these studies need to be confirmed in a prospective study in a larger group of patients, this could become an important screening assay for women and could lead to new therapies to prevent breast cancer.”


Dr. Cavalieri said one of the major obstacles in cancer research is related to the concept that cancer is a problem of 200 diseases — a viewpoint that has impeded researchers from looking at the origin of cancers because the search would be prohibitively complex.


While the expression of various cancers coincides with the concept of 200 diseases, some scientists consider there to be a common origin for many prevalent types of cancer. There is widespread agreement in the scientific community that cancer is triggered by genetic mutations in critical genes, he said.


“The article is the best example of translational research. They have generated a unified concept of carcinogenesis and obtained a practical marker detectable in the urine of breast cancer patients,” said Jose Russo, M.D., senior member, at the Fox Chase Cancer Center in Philadelphia. “This article provides the adequate setting to explore this concept further by laying the basis to prepare a set of prospective clinical trials testing the preventive effects of the agents or mixtures of agents that can intercept the initiation event in breast or other cancers.”


The work represents a paradigm shift in detection of cancer risk in humans and provides the earliest possible rational marker for prevention strategies and regimens, said David Longfellow, Ph.D., president and chief executive officer of the Toxicology Forum — an international, nonprofit organization devoted to conducting open dialogues about problems in toxicology.


“This work conveys a very exciting message — that breast and prostate cancer risk can be identified years before the development of a tumor and suggests that natural preventive agents may be effectively used to prevent the initiation step in cancer,” Dr. Longfellow said. “Although this is a single manuscript, it is based on an extensive body of work in animal models and humans that consistently supports these findings and is complemented by collaboration with many international cancer scientists.”

February 2008-UNMC physicians on Best Doctors list

by Elizabeth Kumru and Ann Lawlor, UNMC Public Affairs

A total of 280 UNMC physicians, including 150 full and part-time faculty, have been recognized on this year’s list of the Best Doctors in America.


The Best Doctors in America 2007-2008 database contains the names and professional profiles of approximately 35,000 physicians in the United States in more than 40 specialties, or the top 3 percent to 5 percent of specialists in the country.


“Our UNMC faculty are truly outstanding clinicians. The Best Doctors recognition once again reaffirms that our patient care and teaching facility is world-class,” said UNMC Chancellor Harold M. Maurer, M.D.


UNMC College of Medicine Dean John Gollan, M.D., Ph.D., agreed.


“Quality patient care is a top priority,” he said. “As an academic health sciences center, our faculty stay abreast of the latest medical advances and are involved in discovering new therapies. Our patients receive exceptional care and our students train with, and learn from, the best.”


“Our UNMC faculty are truly outstanding clinicians. The Best Doctors recognition once again reaffirms that our patient care and teaching facility is world-class.”

UNMC Chancellor Harold M. Maurer, M.D.


The UNMC physicians practice at UNMC’s hospital partner, The Nebraska Medical Center.


Physicians are selected on the basis of the question: “If you or a loved one needed a doctor in your specialty, to whom would you refer them?” A peer-review survey by thousands of doctors determines the doctors included in the database. Only those doctors who earn the consensus support of their peers are included and only physicians in the Best Doctors database are allowed to receive the survey, nominate others and vote.


Two renowned physicians affiliated with Harvard Medical School founded Best Doctors in 1989. Today, it is among the leading resources for more than 10 million people in 30 countries who are seeking expert medical resources and guidance to treat illnesses and injuries of all kinds.


Among the UNMC physicians featured in the Best Doctors in America 2007-2008 database:


Full and part-time faculty


Hurlbert, Barbara – Anesthesiology
Tinker, John – Anesthesiology


Caudill, Christopher – Cardiovascular Disease
Easley, Arthur – Cardiovascular Disease
Niebauer, Mark – Cardiovascular Disease
Porter, Thomas – Cardiovascular Disease
Windle, John – Cardiovascular Disease


Hayes, Kristie – Dermatology


Muelleman, Robert – Emergency Medicine


DeSouza, Cyrus – Endocrinology & Metabolism
Goldner, Whitney – Endocrinology & Metabolism
Lane, James – Endocrinology & Metabolism
Larsen, Jennifer – Endocrinology & Metabolism
Mack-Shipman, Lynn – Endocrinology & Metabolism
Neumeister, Amy -Endocrinology & Metabolism


Fruehling, Richard – Family Medicine
Halm, Daniel – Family Medicine
Harrison, Jeffrey – Family Medicine
Mathews, Monty – Family Medicine
Mostek, Debra – Family Medicine
Nasir, Laeth – Family Medicine
Paulman, Paul – Family Medicine
Paulman, Audrey – Family Medicine
Sitorius, Michael – Family Medicine
Smith, John – Family Medicine
Wheatley, Douglas – Family Medicine


Gollan, John – Gastroenterology
Mailliard, Mark – Gastroenterology
McCashland, Timothy – Gastroenterology
Mukherjee, Sandeep – Gastroenterology
Schafer, Daniel – Gastroenterology
Sorrell, Michael – Gastroenterology
Zetterman, Rowen – Gastroenterology


Eberle, Catherine – Geriatric Medicine
Keller, Brenda – Geriatric Medicine
Lyons, William – Geriatric Medicine
Malloy, Timothy – Geriatric Medicine
Potter, Jane – Geriatric Medicine


Vandenberg, Edward – Geriatric Medicine/Family Medicine


Nystrom, Nils – Hand Surgery


Kalil, Andre – Infectious Disease
Preheim, Laurel – Infectious Disease
Rupp, Mark – Infectious Disease


Bessmer, Joel – Internal Med (general)
Neumeister, J. Scott – Internal Med (general)
O’Dell, David – Internal Med (general)
Shehan, Joseph – Internal Med (general)
Tape, Thomas – Internal Med (general)
Wigton, Robert – Internal Med (general)


Buehler, Bruce – Medical Genetics
Schaefer, G. Bradley, Medical Genetics


Armitage, James – Medical Oncology and Hematology
Bierman, Philip – Medical Oncology and Hematology
Cowan, Kenneth – Medical Oncology and Hematology
Haire, William – Medical Oncology and Hematology
Hauke, Ralph – Medical Oncology and Hematology
Kessinger, Margaret Anne – Medical Oncology and Hematology
Reed, Elizabeth – Medical Oncology and Hematology
Vose, Julie – Medical Oncology and Hematology


Follett, Kenneth – Neurological Surgery
Hellbusch, Leslie – Neurological Surgery
Lennarson, Peter – Neurological Surgery
Long, Douglas – Neurological Surgery


Fayad, Pierre – Neurology


Larsen, Paul – Neurology, Child


Berg, Teresa – OB/GYN
Martin, Thomas – OB/GYN
Smith, Carl – OB/GYN


Camras, Carl – Ophthalmology
Gigantelli, James – Ophthalmology


Esposito, Paul – Orthopaedic Surgery
Fehringer, Edward – Orthopaedic Surgery
Garvin, Kevin – Orthopaedic Surgery
Ginsburg, Glen -Orthopaedic Surgery
Hasley, Brian – Orthopaedic Surgery
Mormino, Matthew – Orthopaedic Surgery
Scherl, Susan – Orthopaedic Surgery


Leopold, Donald – Otolaryngology
Lydiatt, Daniel – Otolaryngology
Lydiatt, William – Otolaryngology


Bridge, Julia – Pathology
Chan, Wing C. (John) – Pathology
Cohen, Samuel – Pathology
Greiner, Timothy – Pathology
Hans, Christine – Pathology
Hinrichs, Steven – Pathology
Johansson, Sonny – Pathology
Lele, Subodh – Pathology
Markin, Rodney – Pathology
McComb, Rodney – Pathology
Pirruccello, Samuel – Pathology
Weisenburger, Dennis – Pathology
Wisecarver, James – Pathology


Antonson, Dean – Pediatric Specialist
Coccia, Peter – Pediatric Specialist
Colombo, John – Pediatric Specialist
Corley, Kevin – Pediatric Specialist
Danford, David – Pediatric Specialist
Erickson, Christopher – Pediatric Specialist
Gordon, Bruce – Pediatric Specialist
Gumbiner, Carl – Pediatric Specialist
Kugler, John – Pediatric Specialist
Rizzo, William – Pediatric Specialist
Romero, Jose – Pediatric Specialist
Sammut, Paul – Pediatric Specialist
Warkentin, Phyllis – Pediatric Specialist/Pathology


Finken, David – Pediatrics (general)
Lacroix, Amy – Pediatrics (general)
Lutz, Richard – Pediatrics (general)
Pitner, Sheryl – Pediatrics (general)
Seivert, Patricia – Pediatrics (general)
Snyder, Sheilah – Pediatrics (general)
Stoolman, Sharon – Pediatrics (general)
Walburn, John – Pediatrics (general)


Bandla, Hari – Pediatrics/Family Medicine


Johnson, Perry – Plastic Surgery


Boust, Susan – Psychiatry
Burke, William – Psychiatry
Fleisher, Mark – Psychiatry
Greiner, Carl – Psychiatry
Kratochvil, Christopher – Psychiatry
Roccaforte, William – Psychiatry
Stull, Todd – Psychiatry
Wengel, Steven – Psychiatry


Rennard, Stephen – Pulmonary & Critical Care Medicine
Romberger, Debra – Pulmonary & Critical Care Medicine
Sisson, Joseph – Pulmonary & Critical Care Medicine
Smith, Stephen – Pulmonary & Critical Care Medicine
Von Essen, Susanna – Pulmonary & Critical Care Medicine


Enke, Charles – Radiation Oncology
Zhen, Weining (Ken) – Radiation Oncology


Anderson, Joseph -Radiology
Apker, Kimberly – Radiology
Gurney, Jud – Radiology
Imray, Thomas – Radiology
Moore, Timothy – Radiology
Walker, Craig – Radiology


Klassen, Lynell – Rheumatology
Mikuls, Ted – Rheumatology
O’Dell, James – Rheumatology


Barkoukis, Teri – Sleep Medicine


Baxter, B. Timothy – Surgery
Langnas, Alan – Surgery
Lynch, Thomas – Surgery
Shaw, Jr., Byers – Surgery
Sudan, Debra – Surgery


Smith, Russell – Surgery/Otolaryngology


Edney, James – Surgical Oncology


Duncan, Kim – Thoracic Surgery
Lackner, Rudy – Thoracic Surgery
Quader, Mohammed – Thoracic Surgery


UNMC volunteer faculty


Hopp, Russell – Allergy and Immunology
Kettelhut, Brett – Allergy and Immunology
Nilsson, Thomas – Allergy and Immunology
Tracy, James – Allergy and Immunology


Hutton, Kent – Anesthesiology
Kugler, Jane – Anesthesiology


Gard, Joseph – Cardiovascular Disease


Spry, Leslie – Clinical Pharmacology, Nephrology


Blatchford, Garnet – Colon and Rectal Surgery
Pitsch, Jr., Richard – Colon and Rectal Surgery


Basler, Rodney – Dermatology
Braddock, Suzanne – Dermatology
Huerter, Christopher J. – Dermatology
Sutton, Margaret – Dermatology


Wahl, Timothy – Endocrinology & Metabolism


Fitzgibbons, William – Family Medicine
Haeberle, John – Family Medicine
Hoelting, David – Family Medicine
Knerl, Jeffrey – Family Medicine
McCoy, Michael – Family Medicine
Settje, Gary – Family Medicine
Zink, Dorothy – Family Medicine


Dyke, David – Gastroenterology
Schafer II, Edwin – Gastroenterology


Scholer, Susan – Geriatric Medicine


Michels, Dale – Geriatric Medicine, Family Medicine


Cochran, Robert – Hand Surgery


Bittner, Marvin – Infectious Disease
Gorby, Gary – Infectious Disease


Bailey, Steven – Internal Med (general)
Bohart, Andrew – Internal Med (general)
Cannella, John – Internal Med (general)
Hoesing, John – Internal Med (general)
Holmes, T.J. – Internal Med (general)
Hranac, Richard – Internal Med (general)
Olson, David – Internal Med (general)
Osterholm, Richard – Internal Med (general)
Policky, David – Internal Med (general)
Shiffermiller, William – Internal Med (general)
Stivrins, Timothy – Internal Med (general)


Schmidt, Michael – Medical Genetics/Pediatrics (general)


Block, Margaret – Medical Oncology and Hematology
Commers, James – Medical Oncology and Hematology
Copur, M. Sitki – Medical Oncology and Hematology
Hutchins, Mark – Medical Oncology and Hematology
Moravec, Jr., Daniel – Medical Oncology and Hematology
Silberstein, Peter – Medical Oncology and Hematology
Verdirame, Joseph- Medical Oncology and Hematology


Gelber, Benjamin – Neurological Surgery
Greene, George – Neurological Surgery
Pierson, Eric – Neurological Surgery


Bertoni, John – Neurology
Birkmann, Lewiston – Neurology
Bobenhouse, James – Neurology
Frankel, Harris – Neurology
Pattee, Gary – Neurology


Bassett, Craig – OB/GYN
Buckley, Krynn – OB/GYN
Gibbens, Donald – OB/GYN
Knolla, Michelle – OB/GYN
Legino, Lonny – OB/GYN
Schulte, Raymond – OB/GYN
Westcott, Susan – OB/GYN


Halsted, Michael – Ophthalmology
Sutton, Gregory – Ophthalmology
Troia, Robert – Ophthalmology
Troia, Sebastian – Ophthalmology
Whitted, Peter – Ophthalmology


Brown, David – Orthopaedic Surgery
Burt, Charles – Orthopaedic Surgery
Canedy, James – Orthopaedic Surgery
Fitzgibbons, Timothy – Orthopaedic Surgery
Goebel, Mark – Orthopaedic Surgery
Hutton, Kirk – Orthopaedic Surgery
McMullen, Scott – Orthopaedic Surgery


Emanuel, Jane – Otolaryngology
Goble, Richard – Otolaryngology
Goebel, Debora – Otolaryngology
Lusk, Rodney – Otolaryngology
Nabity, Thomas – Otolaryngology
Nissen, Alan – Otolaryngology
Quinlan, Trent – Otolaryngology


Mysore, Mohan – Pediatric Specialist
Reynolds, George – Pediatric Specialist
Vanderhoof, Jon – Pediatric Specialist


Wilson, Mark – Pediatric Specialist/Allergy & Immunology


Bleicher, Stacie – Pediatrics (general)
Brabec, Bradford – Pediatrics (general)
Brown, Larry – Pediatrics (general)
Domet , Mark – Pediatrics (general)
Ebers, Douglas – Pediatrics (general)
Gasseling, Philip – Pediatrics (general)
Germer, Michael – Pediatrics (general)
Harrison, Francis – Pediatrics (general)
Higgins, Karen – Pediatrics (general)
Kaufman, David – Pediatrics (general)
Kinberg, Jo Ann – Pediatrics (general)
Koch, Robert – Pediatrics (general)
Krenzer, Kari – Pediatrics (general)
Kronberg, Kent – Pediatrics (general)
Lerner , Gary – Pediatrics (general)
Mikuls, Mary Jane – Pediatrics (general)
Moore, John – Pediatrics (general)
Nelson, Paul – Pediatrics (general)
Nielsen, Laura – Pediatrics (general)
Severson, Gregory – Pediatrics (general)
Shaffer, Kenton – Pediatrics (general)
Stephenson, Betsy – Pediatrics (general)
Straley, Joseph – Pediatrics (general)
Swisher, William – Pediatrics (general)
Willman, Brent – Pediatrics (general)
Woodford, Robert – Pediatrics (general)


Edney, John – Plastic Surgery
Heieck, John – Plastic Surgery
Stice, R. Coleen – Plastic Surgery


Bhatia, Shashi – Psychiatry
Chu, Chung-Chou – Psychiatry
Malin, Paula Jo – Psychiatry
Marcil, William – Psychiatry
Wilson, Daniel – Psychiatry


Floreani, Anthony – Pulmonary & Critical Care Medicine


Nelson, Nick – Radiology


Palmer, William – Rheumatology


Cole, Timothy – Surgery
Kingston, Timothy – Surgery
Raynor, Stephen – Surgery
Voigt, David – Surgery
Waltke, Eugene – Surgery


Thorson, Alan – Surgical Oncology/Colon & Rectal Surgery