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May 2009
Research Could Lead to More Effective Chemotherapy for Neurofibromatosis
Researchers are getting closer to outsmarting one of the most aggressive cell forms in neurofibromatosis (NF)-related tumors.
Through a collaboration with the DCRI, Dr. Mark Slomiany is investigating a way to reduce the chemotherapy-resistance of peripheral nerve sheath tumors (MPNST), NF-related cells that are inherently resistant to treatment.
Surgery and chemotherapy can often slow these cells down, but tumors usually recur at the original site or metastasize to the lungs and other organs, says Dr. Slomiany, research assistant professor in the Department of Cell Biology & Anatomy. His recent findings could mean that chemotherapy becomes a much more effective treatment for NF patients like Conor McManus (see feature story, above), who suffer from dangerous tumor growth.
Collaborating with Drs. Bryan Toole, also of Cell Biology, and Bernard Maria in the DCRI, Dr. Slomiany has shown that antagonizing hyaluronan, which richly coats MPNST cells, can suppress MPNST tumor growth.
Hyaluronan (HA) is believed to promote the growth, invasiveness and resistance of MPNST cells. The suppressive hyaluronan oligomers (o-HA) not only reduce cell growth, they also prevent MPNST cells from pumping out chemotherapeutic agents. "Thus, they sensitize MPNST cells to chemotherapeutic agents," explains Dr. Slomiany.
Dr. Slomiany's work builds on the prior findings of Dr. Bryan Toole's lab, which first identified hyaluronan as a culprit. Dr. Toole has previously demonstrated the efficacy of small fragments of o-HA in suppressing malignant properties in a variety of in vitro and in vivo systems.
Crucial to these findings was the collaboration with Dr. Larry Sherman of Oregon Health and Science University, who contributed his extensive knowledge of primary Schwann cell tumors and MPNSTs.
"This project is a critical translational step from our present level of knowledge about HA mechanisms in cell lines to using o-HA for treatment of NF tumors, including MPNST," notes Dr. Slomiany.
The potential impact of o-HA in treating human cancers is substantial, he says, because they are non-toxic and non-immunogenic.
The results of Dr. Slomiany's research are soon to be published in the scientific research journal, Cancer Research, under the title, "Abrogating Drug Resistance in Malignant Peripheral Nerve Sheath Tumors by Disrupting Hyaluronan-CD44 Interactions with Small Hyaluronan Oligosaccharides."
Slomiany and his team plan to pursue funding through the Children's Tumor Foundation, with hopes for eventual support for pilot human clinical trials.
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Inderjit Singh, PhD
Scientific Director
Darby Children's Research Inst. |
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Bernard L. Maria, MD, MBA
Executive Director
Darby Children's Research Inst. |
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