Dr. Ghassan M. Saed
Associate Professor of Gynecologic Oncology
Director of Translational Research
C.S. Mott Center for Human Growth and Development
Departments of Obstetrics and Gynecology and Oncology
Member of Tumor Biology and Microenvironment Program
Karmanos Cancer Institute
Wayne State University School of Medicine
The discovery of monomeric myeloperoxidase (MPO) expression in Ovarian Cancer.
Our laboratory’s primary research has focused on investigating the role of oxidative stress in the pathogenesis of epithelial ovarian cancer (EOC) for many years. We were the first to report that myeloperoxidase (MPO), is expressed by EOC cells and tissues. This finding was surprising as MPO, an abundant hemoprotein, was known to be present solely in neutrophils and monocytes and plays an essential role in immune surveillance and host defense mechanisms. Notably, the expression of MPO in ovarian cancer has also been confirmed by others, and subsequently we have characterized chemoresistant EOC cells to manifest a further upregulation of MPO. Additional findings from our laboratory highlighted the potential benefits of the combination of serum MPO and free iron as biomarkers for early detection and prognosis of ovarian cancer. We have also reported a cross-talk between MPO and inducible nitric oxide synthase (iNOS), a key pro-oxidant enzyme, as a key mechanism of decreased apoptosis in EOC cells. In this mechanism, MPO utilizes nitric oxide (NO), produced by iNOS, as a one-electron substrate that generates nitrosonium cation, a labile nitrosating species, that increases S-nitrosylation of caspase-3.
The discovery of a unique and novel integrin expression in Ovarian Cancer.
Recently we have discovered a novel integrin heterodimer, αV/β1, in EOC cells. The integrin aV/b1 heterodimer is a known receptor for vitronectin, fibronectin and fibrinogen. Integrin subunits αV and b1 have been previously reported to be individually expressed in ovarian cancer, though the heterodimer has yet to be identified. It has been reported that the enhanced expression of αV or b1 integrin subunits is associated with poor prognosis in subsets of ovarian tumors, and that b1 subunit expression decreases with increasing grade of ovarian carcinoma. Furthermore, we have shown that targeting αV or β1 subunits utilizing monoclonal antibodies induces cytotoxicity in EOC cells. More importantly, we have shown that monomeric MPO binds αV/β1 and serves as a mechanism of survival in EOC cells.
The discovery of a specific target and a specific peptide that selectively induce cytotoxicity in all ovarian cancer cells but not in normal cells.
We have now identified a peptide that selectively kills ovarian cancer cells in vitro without affecting normal cells. This finding was protected by a recent Wayne State University patent which is now licensed to Temple Pharmaceutical.