Newswise — Survivin, a molecule highly expressed in malignant tumor cells and even some chronic autoimmune disorders, is known for promoting tumor cell growth. Researchers at Columbus Children's Research Institute (CCRI) on the campus of Columbus Children's Hospital have now developed a selective biological target that interferes with the expression of survivin, causing a reduction in tumor growth. Further, the preliminary research also shows this molecule has no adverse effects on normal cells, suggesting this type of treatment could mean fewer side effects for people suffering from cancer. The findings were recently published in the Journal of Medical Genetics.
"For our study, we used small interfering RNA molecules (siRNA) to essentially seek out and destroy only the survivin, a molecule we know mainly functions to 'feed' the tumor cells," said Rachel Altura, M.D., the Center for Childhood Cancer at CCRI and assistant professor in the Department of Pediatrics at The Ohio State University College of Medicine and Public Health. "When injected directly into the tumor, or intravenously, the siRNAs interfered with survivin's function and thus, we saw a 70 percent reduction of the tumor growth in our study." Though survivin is expressed in many forms of cancer from ovarian to leukemia, to test the survivin-targeted therapies in tumors, Altura's group looked at rhabdomyosarcoma, a particularly aggressive form of muscle cancer that would quickly show results of their work. Specifically, 63 rhabdomyosarcoma tumor samples were aligned on slides to identify those tumors expressing survivin. Of those samples, more than 80 percent expressed survivin. Next, red fluorescent clones of the human rhabdomyosarcoma cells were replicated in an animal model and then treated with an injection of survivin-siRNA-encoding plasmids. The 70 percent reduction in the tumor growth was seen over two weeks.
As part of the follow-up research, Altura's group, including research associate Mike Holloway and post-doctoral fellow Hugo Caldas, plans to further evaluate the siRNAs in normal cells to confirm the study's suggested benefit of fewer side effects. Additionally, they plan to look at long-term expression and delivery methods for brain tumors. The CCRI research was funded in part by a grant from Hope Street Kids.
Columbus Children's ranks among the top 10 in National Institutes of Health research awards and grants to freestanding children's hospitals in the country and houses the Department of Pediatrics of The Ohio State University College of Medicine and Public Health. With nearly 600,000 patient visits each year, Children's Hospital is a 112-year-old pediatric healthcare network treating newborns through age 21. In 2004, the Columbus Children's Research Institute conducted more than 300 research projects and is the home of Centers of Emphasis encompassing gene therapy; molecular and human genetics; vaccines and immunity; childhood cancer; cell and vascular biology; developmental pharmacology and toxicology; injury research and policy; microbial pathogenesis; cardiovascular medicine; and biobehavioral health. Pediatric Clinical Trials International (PCTI), a site management organization affiliated with the hospital, also coordinated more than 50 clinical trials. In addition to having one of the largest ambulatory programs in the country, Children's offers specialty programs and services. More than 75,000 consumers receive health and wellness education each year and affiliation agreements with nearly 100 institutions allow more than 1,700 students and 500 residents to receive training at Children's annually. More information on Children's Hospital of Columbus is available by calling (614) 722-KIDS (5437) or through the hospital's Web site at http://www.columbuschildrens.com.
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