Development of COX inhibitors in cancer prevention and therapy.

Gastrointestinal & Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, Bethesda, Maryland 20892-7317, USA.
American journal of clinical oncology (Impact Factor: 2.21). 09/2003; 26(4):S48-57. DOI: 10.1097/01.COC.0000074157.28792.02
Source: PubMed

ABSTRACT On the strength of in vitro, in vivo, observational, and clinical data, nonsteroidal antiinflammatory drugs (NSAIDs)-also referred to as COX inhibitors-have emerged as lead compounds for cancer prevention, and possible adjuncts to cancer therapy. Thus far, the routine use of NSAIDs for these indications is limited, largely owing to toxicity concerns, the paucity of efficacy data for any specific target organ, and uncertainties with regard to the most appropriate regimen (i.e., the best agent, formulation, dose, route of administration, and duration). Strategies to address these concerns primarily aim to improve the therapeutic index (i.e., benefit:risk ratio) of COX inhibitors by 1) minimizing systemic exposures whenever feasible, 2) achieving greater mechanistic specificity, 3) coadministering agents that provide prophylaxis against common toxicities, and 4) coadministering other effective anticancer agents. Clinical trials testing most of these strategies have been completed or are under way. The National Cancer Institute has a substantial research portfolio dedicated to the identification, testing, and development of NSAIDs as preventive and therapeutic anticancer agents. Discovering how to apply NSAIDs in persons with-or at risk for-cancer, although challenging, has the potential for considerable clinical and public health benefits.

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    ABSTRACT: PURPOSE: to evaluate the expression of cyclooxygenase-2 (COX-2) in ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), adjacent normal stroma, and epithelium. The correlation of expression levels with nuclear grade, histological grade, presence or absence of comedonecrosis, tumor size, and patient age was also analyzed. METHODS: forty-seven surgical samples obtained from mastectomy and quadrantectomy with simultaneous DCIS and IDC, stages I and II were included. Anti-COX-2 polyclonal antibodies were used to determine enzyme expression. Samples were classified from zero to three, in accordance with number and intensity of stained cells. RESULTS: COX-2 was positively expressed in IDC, DCIS, and normal epithelium in 86.7, 84.4, and 73.3% of the cases, respectively. Concerning nuclear grade (NG), COX-2 expression was positive in 80% of cases of NG-I; in 81.5 and 78.9% of NG II, and in 88.5 and 96.1% of NG III in DCIS and IDC, respectively. COX-2 expression occurred in 78.9% of DCIS with comedonecrosis and in 89.3% without comedonecrosis. As to histological grade (HG) of IDC, COX-2 was positive in 83.3% of HG-I; 89.9% of HG-II and 80% of HG-III. Concerning tumor diameter, COX-2 was present in 86.1% of IDC cases and in 83.3% of DCIS larger than 2 cm and in 11% of IDC and DCIS tumors ≤2 cm. The age range ≥50 years presented 90% expression for IDC and 86.7% for DCIS, and the expression was 92.5% for both IDC and DCIS in patients <50 years. CONCLUSIONS: our results demonstrated high correlation between COX-2 expression in IDC, DCIS and in the normal epithelium, which is consistent with the hypothesis that COX-2 over expression is an early event in breast carcinogenesis. There was no significant correlation between COX-2 expression in IDC and DCIS and nuclear grade, histological grade, presence of comedonecrosis, age group and tumor size.
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    ABSTRACT: This study was done to evaluate the association of cyclooxygenase 2 (COX-2) and brain fatty acid binding protein (BFABP) with tumor grade and outcome of grades I-II meningiomas treated with radiotherapy. From 1996 to 2008, 40 patients with intracranial grades I-II meningiomas were treated with radiotherapy. Immunohistochemical staining for COX-2 and BFABP were performed on formalin-fixed paraffin-embedded tissues. COX-2 expression was significantly associated with BFABP status and both COX-2 (P < 0.01) and BFABP (P = 0.01) expression were stronger in the grade II meningiomas than in grade I tumors. Among the clinicopathologic factors, age and COX-2 status were prognostic in progression-free survival. Patients with moderate or strong COX-2 expression had worse outcome than those with negative or weak COX-2 expression (P = 0.03) after controlling for potential confounders. Our results suggest that the molecular biomarker COX-2 has prognostic significance in intracranial grades I-II meningiomas following radiotherapy.
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