Ghassan Saed's Laboratory

Highlights of Dr. Saed's lab

 

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.

Breakthrough research

Patents

COMPOSITIONS AND METHODS TO TREAT SOLID TUMORS

Publication Number: 20170121410
Abstract: Compositions and methods that utilize anti-CD11b antibodies, anti-CD18 antibodies, anti-myeloperoxidase (MPO) antibodies, anti-integrin alpha-V antibodies, anti-integrin beta-1 antibodies, Abciximab, neutrophil inhibitory factor (NIF) protein, and/or combinations thereof to treat solid tumor cancers are described.
Type: Application
Filed: October 28, 2016
Publication Date: May 4, 2017
Applicant: Wayne State University
Inventor: Ghassan M. Saed

METHOD OF PREVENTING ADHESIONS BY APOPTOSIS OF ADHESION PERITONEAL CELLS

Publication Number: 20040131600
Abstract: Methods for the prevention of adhesion formation and development involve the administration of therapeutic formulations to a patient which modulates the rate of apoptosis of adhesion fibroblast cells. The formulations preferably include Bax, Bax enhancers, such as p53, Bax agonists, Bcl-2 inhibitors and Bcl-2 antagonists. A method is also provided for determining the predisposition of a subject to adhesion formation by measuring the Bcl-2/Bax ratio at multiple sites within the subject.
Type: Application
Filed: March 1, 2004
Publication Date: July 8, 2004
Inventor: Ghassan M. Saed

MODEL FOR IN VITRO ADHESION DEVELOPMENT

Publication Number: 20040096817
Abstract: A biological model for the development of adhesions in vitro comprises a pair of opposed surfaces of tissue explants maintained in a culture media for a sufficient time and under conditions to permit the formation of adhesions. The model is useful for evaluating compounds and techniques for the prevention and remediation of adhesions, and for individualizing the therapeutic options for patients who may experience adhesions.
Type: Application
Filed: May 28, 2003
Publication Date: May 20, 2004
Applicant: Wayne State University
Inventor: Ghassan M. Saed

METHODS OF TREATING CANCER WITH CD 11B ANTIBODIES

International Publication Number: WO 2010/017083 AI
International Publication Date: February 11, 2010
Description of Patent: Methods and compositions for treating cancer with CDI Ib antibodies are disclosed. The antibodies may be WT.5 antibodies or compete with WT.5 antibodies, and induce apoptosis in SKOV, MDAH-2274, or BxPC-3 cells.
Inventor: Ghassan M. Saed

METHOD OF PREVENTING ADHESIONS WITH INTERFERON-GAMMA

International Publication Number: WO 02/072016 A3
International Publication Date: September 19, 2002
Description of Patent: Methods for the prevention of adhesion formation and development involve the administration of therapeutic formulations to a patient which include, as active ingredients, IFN-ʸ or IFN-ʸ enhancers. The IFN-ʸ or IFN-ʸ enhancers are preferably administered to fibrosis tissues in a subject prior to an event which induces adhesion formation, such as a surgical event.
Inventor: Ghassan M. Saed

METHODS FOR THE PREVENTION OF ADHESION FORMATION AND DEVELOPMENT

Patent Number: US2006025364
Application Number: US20050081278
Application Date: March 16, 2005
Publication Date: February 2, 2006
Description of Patent: Methods for the prevention of adhesion formation and development, and for the stimulation of fibrosis, involve the administration of therapeutic formulations to a patient containing inhibitors or stimulators to selected molecular adhesion markers. The molecular markers of the invention include Caspase 2, Caspase 3, Caspase 9, PPAR alpha, PPAR beta, PPAR gamma1, PPAR gamma2, and NF-kappa B.
Inventor: Ghassan M. Saed