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Release: Dec. 3, 2001

UI researchers receive cancer grants for collaborative studies

IOWA CITY, Iowa -- University of Iowa researchers working on four different cancer-related studies have received year 2001 Translational/Collaborative Research Grants made through the Holden Comprehensive Cancer Center at the UI.

These awards help faculty develop translational projects, which are investigations that involve transferring basic research findings into practical applications. The following investigators received one-year, $20,000 awards, effective Dec. 1, for their studies:

Frederick Domann, Ph.D., UI associate professor of radiation oncology, is principal investigator for "Pre-clinical Studies of DNA Methyltransferase Inhibitors for Cancer Therapy." Methylation is the addition of single carbon atoms to specific DNA sites. Alterations in normal DNA methylation patterns are an early and important event in cancer progression.

Domann said the long-term goal of his team's project is to address whether drug-based inhibitors of the enzymes that control the DNA methylation process can decrease the rate of tumor progression and thus prolong the period of disease-free survival. He said, "Our current proposal addresses whether aberrant DNA methylation occurs within specific genes in human cancers, especially pheochromocytoma and neuroblastoma, and whether the extent of methylation and the cancer's malignant properties can be affected by inhibitors of DNA methylation." M. Sue O’Dorisio, M.D., Ph.D., UI Foundation Professor of Pediatrics, is co-investigator on the project.

Wendy Maury, Ph.D., UI assistant professor of microbiology, and C. Michael Knudson, M.D., Ph.D., UI assistant professor of pathology, co-principal investigators, shared an award for "Retrovirus-induced Apoptosis." Infection with retroviruses such as HIV and HTLV can cause cancer in humans. This project addresses how retroviruses induce cell death (also called apoptosis) following infection. The study also will examine the role of p53, a gene that normally functions as a tumor suppressor but is mutated in nearly 50 percent of human cancers.

Jose Morcuende, M.D., Ph.D., UI assistant professor of orthopaedic surgery, is leading a study on "Comprehensive Analysis of Gene Expression using SAGE from Paraffin-Block isolated mRNA." This project will evaluate the feasibility of extracting RNA that has been stored in paraffin blocks and will attempt to use this RNA for comprehensive gene expression profiling. Analyzing this type of stored material for gene expression could provide information that can be compared to the already known clinical course of patients, with the potential for more accurate cancer diagnoses and prognoses, Morcuende said.

UI collaborators on this study include Bento Soares, Ph.D., professor of pediatrics, physiology and biophysics, and biochemistry; Barry DeYoung, M.D., associate professor of pathology and orthopaedic surgery; Sergey Malchenko, M.D., Ph.D., assistant research scientist in pediatrics; and Thomas Casavant, Ph.D., professor of electrical-computational bioengineering.

Douglas Spitz, Ph.D., UI associate professor of radiation oncology, is principal investigator for "Metabolic Oxidative Stress and Cancer Therapy." This collaborative study aims to provide a biochemical rationale for developing new cancer therapies by combining drugs and dietary changes already approved for use in humans. The project will determine if therapies designed to inhibit glucose metabolism and hydroperoxide detoxification, combined with manipulations that increase mitochondrial metabolism, will preferentially kill tumor cells (without harming normal cells) via metabolic oxidative stress. Initially, the project will test these concepts in cell culture, and successful drug combinations will then be tested in clinical trials.

In addition to Spitz's basic science work, collaboration on this study includes the basic science work of Larry Oberley, Ph.D., UI professor of radiation oncology and director of the Free Radical and Radiation Biology Program, and the clinical work of Raymond Hohl, M.D., Ph.D., UI associate professor of internal medicine and director of the Division of Hematology, Oncology and Blood and Marrow Transplantation.

The Holden Comprehensive Cancer Center is Iowa's only National Cancer Institute (NCI)-designated comprehensive cancer center. NCI-designated comprehensive cancer centers are recognized as the leaders in developing new approaches to cancer prevention and cancer care, conducting leading edge research and educating the public about cancer. Visit the cancer center online at http://www.uihealthcare.com/depts/cancercenter.

University of Iowa Health Care describes the partnership between the UI College of Medicine and the UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at http://www.uihealthcare.com/.