Study of cyclooxygenase-2 in renal cell carcinoma.
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: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.06/2012; 46(3):237-45. DOI:10.4132/KoreanJPathol.2012.46.3.237
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ABSTRACT: Appropriate use of multiple reliable molecular biomarkers in the right context will play a role in tailor-made medicine of clear cell renal cell carcinoma (RCC) patients in the future. A total of 11,056 patients from 53 studies were included in this review. The article numbers of the each evidence levels, using the grading system defined by the Oxford Centre for Evidence-based Medicine, in 1b, 2a, 2b, and 3b were 5 (9 %), 18 (34 %), 29 (55 %), and 1 (2 %), respectively. The main goal of using biomarkers is to refine predictions of tumor progression, pharmacotherapy responsiveness, and cancer-specific and/or overall survival. Currently, carbonic anhydrase (CA9) and vascular endothelial growth factor (VEGF) in peripheral blood and p53 in tumor tissues are measured to predict metastasis, while VEGF-related proteins in peripheral blood are used to assess pharmacotherapy responsiveness with sunitinib. Furthermore, interleukin 8, osteopontin, hepatocyte growth factor, and tissue inhibitors of metalloproteinases-1 in peripheral blood enable assessment of responsiveness to pazopanib treatment. Other reliable molecular biomarkers include von Hippel-Lindau gene alteration, hypoxia-inducible factor-1α, CA9, and survivin in tumor tissues and VEGF in peripheral blood for predicting cancer-specific survival. In the future, studies should undergo external validation for developing tailored management of clear cell RCC with molecular biomarkers, since individual institutional studies lack the generalization and consistency required to maintain accuracy among different patient series.Clinical and Experimental Metastasis 08/2013; DOI:10.1007/s10585-013-9612-7 · 3.73 Impact Factor