Research papers
2000 · Annual Review of Biochemistry · 2,928 citations
The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.
1998 · The FASEB Journal · 2,512 citations
Cyclooxygenase (COX), the key enzyme required for the conversion of arachidonic acid to prostaglandins was first identified over 20 years ago. Drugs, like aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in biology and disease than at any other time in history. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Here, we summarize the current understanding of the role of cyclooxygenase-1 and -2 in different physiological situations and disease processes ranging from inflammation to cancer. We have attempted to include all of the most relevant material in the field, but due to the rapid progress in this area of research we apologize that certain recent findings may have been left out.
2012 · Annals of African Medicine · 38 citations
BACKGROUND: Compared to the developed world, there are relatively few studies that describe the tumor biology of breast cancer in African women. While little is known about the tumor biology, clinical and epidemiologic studies suggest that breast cancer in African women are characterized by presentation at late stage and poor clinical outcomes. Analysis of the biological features of breast cancers in Nigerian women was designed to bring additional insight to better understand the spectrum of disease, the phenotypes that present, and the types of interventions that might improve outcomes. MATERIALS AND METHODS: We performed histological analyses for hormone receptors (estrogen and progesterone receptors), HER2, and tumor infiltrating macrophages (TAM) on 17 breast cancers, obtained from Abia State University Teaching Hospital (Aba, Nigeria), between November 2008 and October 2009. On a subset of these cases, we investigated the potential role of a virus in the etiology of these aggressive cancers. RESULTS: The majority of cases in this cohort were characterized as high grade (100% were grade III), triple-negative (65%), and occur in young women (mean age 47 years). We observed high infiltration of TAMs in these tumors, but no evidence of a viral etiology. CONCLUSION: Our findings indicate that breast cancers in Nigerian women have a highly aggressive phenotype (high grade, hormone receptor negative), which is similar to other studies from Africa and other developing nations, as well as from African American women, but is significantly different from Caucasian women in the developed world. The presence of high numbers of TAMs in these tumors raises the possibility of targeting the immune microenvironment for therapeutic interventions.