Study of cyclooxygenase-2 in renal cell carcinoma

Department of Urology, Osaka City University Hospital, Abenoku, Osaka 545-8585, Japan.
International Journal of Molecular Medicine (Impact Factor: 1.88). 03/2004; 13(2):229-33. DOI: 10.3892/ijmm.13.2.229
Source: PubMed

ABSTRACT Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenetic function. As the expression of COX-2 is up-regulated in human colorectal carcinoma and other cancers, we investigated the expression of COX-2 in human renal cell carcinoma (RCC) tissues. One hundred and eight specimens were obtained from patients with RCC, and 20 from normal kidney (NK) tissues. Immunohistochemistry, using affinity purified anti-bodies against human COX-2, and RT-PCR to study the COX-2 mRNA expression were carried out. We also examined whether or not there was a significant difference in the expression of COX-2 among grades (G1, G2, G3) and stages (pT1, pT2, pT3a, pT3b) in RCC. While no marked expression of COX-2 was observed in the NK tissues, a significantly strong expression of COX-2 was detected in RCC tissues. The extent and intensity of immunoreactive COX-2 polypeptides in cancer cells were statistically greater than those of cells from normal kidney tissues. However, no marked difference was seen among grades or between stages. These results demonstrate that the generated COX-2 in human renal cell carcinoma plays an important role in the proliferation of malignant renal cells.

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    ABSTRACT: Cyclooxygenase-2 (COX-2) plays a major role in the development of cancer through numerous mechanisms. COX-2 is expressed in the majority of renal cell carcinoma (RCC) tumors and correlates with stage, grade, and microvessel density. Based on potential additive or synergistic antitumor effects, interferon-alpha (IFNalpha) and celecoxib, an oral COX-2 inhibitor, were given to metastatic RCC patients in a Phase II trial. Patients with untreated, metastatic RCC received IFNalpha 3 million units (MU) daily and celecoxib 400 mg orally (p.o.) twice daily continuously until disease progression or unacceptable toxicity. Pretreatment, paraffin-embedded RCC tumor samples were immunohistochemically stained for COX-2 expression and plasma basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were assayed to determine predictive or prognostic potential. There were three partial responses among 25 patients treated (objective response rate, 12%; 95% confidence interval [CI], 3-31%). The observed median time to disease progression (TTP) for the entire cohort was 3.3 months. A significant association between maximal COX-2 staining and clinical response was observed: all patients who experienced an objective response demonstrated 3+ COX-2 tumor immunostaining (trend test: P=0.03). Therapy was well tolerated without cardiac or other notable toxicity. The addition of celecoxib to IFNalpha did not increase the objective response rate or TTP of this unselected cohort. Maximal COX-2 tumor immunostaining may identify RCC patents more likely to achieve clinical benefit with COX-2 inhibition in combination with IFNalpha. Further investigation of this combination in 3+ COX-2-overexpressing RCC tumors is warranted.
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