Overexpression of cyclooxygenase‐2 in high‐grade human transitional cell carcinoma of the upper urinary tract

Oku, S.; Higashi, Michiyo; Imazono, Yoshiharu; Sueyoshi, Kazunobu; Enokida, Hideki; Kubo, Hidehumi; Yonezawa, Suguru; Shirahama, Tsuranobu

doi:10.1046/j.1464-410x.2003.03057.x

Cited by 16 publications

(8 citation statements)

References 26 publications

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“…It may be hypothesized that COX‐2 overexpression is involved in the initiation process of carcinogenesis, as shown previously [14,23], but, once tumours have reached a level of aggressiveness (such as in the invasive bladder cancer cases of the present study), the maintenance of COX‐2 expression may be associated with tumours presenting a better prognosis. Furthermore, the evolution of expression of COX‐2 from NMIBT to invasive bladder tumours, compared to tumours that are invasive upfront, is not established and may have contributed to the results obtained.…”

Section: Discussionsupporting

confidence: 71%

Improved cancer specific‐survival in patients with carcinoma invading bladder muscle expressing cyclo‐oxygenase‐2

Aziz¹,

Lessard²,

Moore³

et al. 2010

BJU International

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Immunoreactivity was categorized as positive if COX-2 staining was present in > 5% tumour cells. RESULTSThe expression of COX-2 was not influenced by tumour stage, grade or nodal status, nor any other parameters. The risk factors that influenced disease-specific survival in carcinoma invading bladder muscle on multivariate analysis were lymph node status (hazards ratio, HR = 2.46 for N1, P = 0.001, HR = 2.90 for N2, P < 0.001, HR = 5.19 for N3, P = 0.012), use of neoadjuvant chemotherapy (HR = 3.54; P = 0.004) or adjuvant chemotherapy (HR = 0.57, P = 0.014) and COX-2 expression (HR = 0.64 if > 5% cells had positive expression; P = 0.025). Kaplan-Meier analysis showed an increased disease-specific survival ( P = 0.0063), as well as longer recurrence-free survival ( P = 0.003), in patients with muscleinvasive bladder tumours expressing COX-2 in > 5% of the cells. A tendency was also observed in a subgroup with positive nodes treated with adjuvant chemotherapy ( P = 0.093). CONCLUSIONS

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Section: Discussionsupporting

confidence: 71%

Improved cancer specific‐survival in patients with carcinoma invading bladder muscle expressing cyclo‐oxygenase‐2

Aziz¹,

Lessard²,

Moore³

et al. 2010

BJU International

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“…6,7 Several studies have demonstrated that COX-2 is involved in the development of many tumors by affecting biological features including proliferation, angiogenesis, apoptosis, and adhesion, [9][10][11] and that COX-2 specific inhibitors actually reduce the incidence of development of tumors in animals 12 as well as in humans. 13 The expression of COX-2 is up-regulated in both transitional [14][15][16] and squamous 17 cell carcinoma of the human urothelial tissues.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of 5‐lipoxygenase pathway suppresses the growth of bladder cancer cells

2006

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Aim: Many stimuli, including growth factors and cytokines, activate arachidonic acid (AA) metabolic pathways, which are involved in cancer development and progression. We examined the effects of a series of pharmacological inhibitors of AA metabolic enzymes on bladder cancer cells to determine the role of AA pathway in this malignancy. Methods: Human bladder cancer cell lines were treated with various AA metabolic enzymes inhibitors for lipoxygense (LOX) and cyclooxygenase (COX) pathways, and the growth suppression effects were examined. The enzyme expression in cancer cells was examined by immunoblot analyses. Results: A 5-LOX-specific inhibitor, AA861, dose-dependently inhibited the growth of bladder cancer cells. The growth inhibitory effects were greatly abolished by 5-LOX product, 5-HETE, but not by other LOX products examined. They were observed in four cancer cells that expressed 5-LOX, but not in one that did not. Of a series of LOX and COX pathway inhibitors, AA861 was the strongest one to suppress the growth of cancer cells. Conclusions: Bladder cancer cells frequently expressed 5-LOX. A 5-LOX-specific inhibitor, AA861, revealed the strongest growth suppression of those cells compared to other LOX and COX pathway inhibitors, and the growth suppression effects were considered to be due to inhibition of the enzymatic activity. Therefore, 5-LOX may play a regulatory role in proliferation and/or survival of bladder cancer, and may be a therapeutic target for the disease.

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“…The higher expression level of COX-2 has been shown to increase invasiveness in colon cancer and prostate cancer cells (24,39). For UUTUC, overexpressed COX-2 was also found in patients and was associated with the pathologic stage and grade, indicating that COX-2 may be involved in UUTUC carcinogenesis and development (40,41). The effect of the specific COX-2 inhibitor on AR-enhanced migration and invasion clearly demonstrated the essential role of COX-2 in cell migration and invasion ( Fig.…”

Section: Discussionmentioning

confidence: 98%

Androgen receptor promotes the migration and invasion of upper urinary tract urothelial carcinoma cells through the upregulation of MMP-9 and COX-2

Chen

Hsieh

Chang³

et al. 2013

Oncology Reports

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Dysregulated androgen receptor (AR) signaling is implicated in several types of tumor, including carcinomas of the prostate, breast, liver and bladder. However, the contribution of AR to the progression of upper urinary tract urothelial carcinomas (UUTUC) has not been fully investigated. In the present study, we demonstrated that the AR is involved in the metastasis and invasiveness of UUTUC cells. We investigated the role of the AR in UUTUC by using UUTUC-derived BFTC 909 cells. The overexpression of AR promotes the migration and invasion of BFTC 909 cells. Expression of migration/invasion-related genes was increased in BFTC 909 cells overexpressing AR determined by qPCR and western blot analyses. The results showed that AR-enhanced migration and invasion of UUTUC cells are linked to the upregulation of the matrix-degrading enzyme MMP-9 and cyclooxygenase (COX)-2. Subsequently, the blocking of MMP-9 and COX-2 signaling by inhibitors suppressed AR-enhanced cell migration and invasion. The results of the present study provide evidence for the first time of the role of AR in the motility and invasion of UUT cancer cells and support the hypothesis that the AR may play a critical role in the establishment of the invasive phenotype in urothelial neoplasia of UUT. Thus, the AR may also serve as a novel biomarker and potential therapeutic target for UUT cancer.

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Overexpression of cyclooxygenase‐2 in high‐grade human transitional cell carcinoma of the upper urinary tract

Cited by 16 publications

References 26 publications

Improved cancer specific‐survival in patients with carcinoma invading bladder muscle expressing cyclo‐oxygenase‐2

Improved cancer specific‐survival in patients with carcinoma invading bladder muscle expressing cyclo‐oxygenase‐2

Inhibition of 5‐lipoxygenase pathway suppresses the growth of bladder cancer cells

Androgen receptor promotes the migration and invasion of upper urinary tract urothelial carcinoma cells through the upregulation of MMP-9 and COX-2

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