Shailendra K. Sahu, PhD. under the direction of Vincent C. Traynelis, MD, Professor of Neurosurgery and Timothy Ryken, MD Associate Professor of Neurosurgery, runs the Glioma Research Laboratory (GRL), Department of Neurosurgery, The University of Iowa School of Medicine.

The GRL is involved in pre-clinical feasibility studies of genetic and chemical molecules in animal brain tumor models and in cultured glial tumor cells. The research is carried out in collaboration of scientists from departments of Neurosurgery, Neurology, and Radiation Oncology, University of Iowa. Our primary focus has been on cis-parinaric acid (cPNA) which shows promise in the treatment of malignant gliomas. cPNA is a 4-conjugated polyunsaturated fatty acid which increases oxidative stress and is preferentially cytotoxic to malignant glial cells compared to normal astrocytes. Micromolar concentrations of this compound will destroy human and rodent glial tumor cells yet spares normal astrocytes in culture. We have demonstrated that the signal transduction events of cPNA in malignant astrocytes differs from the known effects of another oxidative agent, hydrogen peroxide. We have also observed that the forkhead transcription factor Foxo3a may be involved in the differential cytotoxicity of cPNA by decreasing the anti-oxidant enzyme, MnSOD in malignant astrocytes and increasing the MnSOD in normal astrocytes for protection from the oxidative stress. Our scientific goal is to understand the mechanism of this differential cytotoxicity in order to achieve a safe and effective treatment for human brain tumors.

We are also interested in other therapies which impact tumor survival and growth through oxidative mechanisms. Most recently we have collaborated with Dr. Larry W. Oberley, to evaluate the therapeutic effectiveness of intracerebral adeno-MnSOD in combination with BCNU and 3-aminotriazole in a brain tumor model in rats. This work demonstrated that adeno-MnSOD significantly increased the survival of 36B10 (a malignant rat astrocytoma) brain tumor bearing rats when administered before BCNU. We are currently engaged in determining the survival benefit of this combined treatments with or without 3-aminotrizole, an inhibitor of catalase enzyme.