Cyclooxygenase-2 and prostate carcinogenesis

Hussain, Tajamul; Gupta, Sanjay; Mukhtar, Hasan

doi:10.1016/s0304-3835(02)00524-4

Cited by 218 publications

(169 citation statements)

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“…COX-2 expression has been reported in prostate cancer tissue. [24][25][26][27] However, there are some exceptions to this observation. Zha et al 30 reported that COX-2 is not consistently overexpressed in prostate cancer and found that proinflammatory atrophic lesions in prostate, which are said to be precursors of prostate cancer, express COX-2.…”

Section: Discussionmentioning

confidence: 97%

“…[20][21][22] Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme that converts arachidonic acid to prostaglandins. 23 A variety of mechanisms have been proposed to explain how COX-2 upregulation affects carcinogenesis, that is, by promoting angiogenesis, 24 by enhancing cellular motility 25 and by increasing cancer cell resistance to apoptosis. 26 Usually, COX-2 expression is either weak or absent in normal prostate tissue and overexpressed in prostate cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

Lorenzo

Placido

Autorino

et al. 2005

Prostate Cancer Prostatic Dis

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Objectives: To determine whether COX-2, bcl-2 and neoangiogenesis are related to human prostate cancer relapse after definitive surgical treatment and progression toward androgen independence and to evaluate the association between the patterns of these tumoral biomarkers and other standard clinico-pathological parameters (such as Gleason score, PSA, TNM stage). Materials and Methods: We retrospectively analyzed the records on 126 prostate cancer samples from patients treated at our University Hospital from 1995 to 2002. The 72 patients with clinically localized disease (group 1) had undergone radical prostatectomy. Another 54 patients (group 2) had metastatic androgen-independent disease. Archived material relating to the subjects was then immunostained for bcl-2, COX-2 and CD-31, using an anti-bcl-2 monoclonal primary antibody, an anti-COX-2 polyclonal rabbit antibody and an anti-CD-31 monoclonal mouse antibody to evaluate neoangiogenesis (MVD, microvessel density). Results: We found that bcl-2, COX-2 and MVD expression increased from group 1 to group 2. The intergroup difference was significant only for high MVD (Po0.05). On the other hand, high MVD, high bcl-2 and high COX-2 expression was correlated with a higher PSA level (Po0.01), whereas only a high MVD was also related with Gleason score (Po0.05). We used univariate analysis to evaluate the prognostic impact of biologic and clinico-pathologic parameters on the diseasefree-survival of 72 patients treated by radical prostatectomy. A total of 30 patients (41.6%) experienced biochemical relapse; bcl-2, COX-2 and MVD significantly correlated with disease relapse in these patients. In fact, we observed disease relapse in 24/45 (53%) with high bcl-2 expression, in 15/21 (71%) with a high MVD count and finally, in 30/58 (52%) with high COX-2 expression. Finally, PSA value and Gleason score were the only two biologic markers significantly associated to disease relapse in a multivariate analysis. Conclusions: Our results strongly support a role for bcl-2, COX-2 and angiogenesis in the development and progression of prostate cancer. Of course, we are aware of the small sample size considered in our study. Further investigations would better clarify the prognostic and therapeutic implications of these findings.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

Lorenzo

Placido

Autorino

et al. 2005

Prostate Cancer Prostatic Dis

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“…38 Earlier studies on immunohistochemistry localization and semiquantitative estimation of COX-2 expression concluded that COX-2 expression has limited association with stage and disease severity (local invasion) but it strongly associates with tumor grade. [10][11][12][13][14][15] On contrary, some reports have dismissed any association with tumor grade and have suggested that COX-2 is expressed by infiltrating lymphocytes and macrophage, which occurs during inflammatory atrophy of the prostate. 27 However, none of these reports analyzed COX-2 expression with respect to biochemical recurrence (i.e., disease progression).…”

Section: Determination Of Sensitivity Specificity Accuracy Ppv Andmentioning

confidence: 99%

“…[10][11][12] Typically, later studies reported low or no expression in normal, benign prostatic hyperplasia or low-grade cancer tissues but elevated levels in prostatic intraepithelial neoplasia (PIN) and high-grade cancer. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] A prominent study, however, discounted COX-2 specific staining in all epithelial tissues and claimed that COX-2 is expressed only in infiltrating lymphocytes and proliferative inflammatory atrophy. 27 Nonetheless, several studies, using experimental models and established prostate cancer cell lines, have established a chemopreventive and antitumor activity of COX-2 inhibitors, implying the putative role of COX-2 in prostate carcinogenesis.…”

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confidence: 99%

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

Cohen

Gómez

Omori

et al. 2006

Intl Journal of Cancer

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Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n 5 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twentythree patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high-or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p 5 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process. ' 2006 Wiley-Liss, Inc.Key words: inflammation; immunohistochemistry; PSA; cancer progression; prognostic indicators; multivariate analysis; tumor markers Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are prostaglandin endoperoxide synthases, which are rate limiting enzymes in the conversion of the fatty acid arachidonic acid into physiologically active eicosanoids such as prostaglandin, thromboxane and prostacyclin. 1 COX-2 is the inducible form of COX that is frequently elevated in cancer tissues. [2][3][4] Although the mechanism of COX-2 action in carcinogenesis or progression is not well established, COX-2 inhibitors have been shown to be chemopreventive in cancer, specifically in colorectal cancer. [5][6][7] The expression and role of COX-2 in prostate cancer has been a topic of several reports over the decade. 8,9 There exists some controversy over the expression, detection and the putative role of COX-2 in prostate carcinogenesis and progression. While early studies reported high-level expression of COX-2 in prostate, findings from subsequent studies have been mixed. [10][11][12] Typically, later studies reported low or no expression in normal, benign prostatic hyperplasi...

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“…Certain types of chronic inflammation such as ulcerative colitis have long been associated with a high risk of cancer development (Coussens and Werb, 2002;Hussain et al, 2003). It is believed that increased free radical generation is one important mechanism that promotes the progression of chronic inflammation into malignant transformation (Hussain et al, 2003).…”

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confidence: 99%

β-Catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells

et al. 2009

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BACKGROUND: Alteration in respiratory activity and mitochondrial DNA (mtDNA) transcription seems to be an important feature of cancer cells. Leukotriene D 4 (LTD 4 ) is a proinflammatory mediator implicated in the pathology of chronic inflammation and cancer. We have shown earlier that LTD 4 causes translocation of b-catenin both to the mitochondria, in which it associates with the survival protein Bcl-2 identifying a novel role for b-catenin in cell survival, and to the nucleus in which it activates the TCF/LEF transcription machinery. METHODS: Here we have used non-transformed intestinal epithelial Int 407 cells and Caco-2 colon cancer cells, transfected or not with wild type and mutated (S33Y) b-catenin to analyse its effect on mitochondria activity. We have measured the ATP/ADP ratio, and transcription of the mtDNA genes ND2, ND6 and 16 s in these cells stimulated or not with LTD 4 . RESULTS: We have shown for the first time that LTD 4 triggers a cellular increase in NADPH dehydrogenase activity and ATP/ADP ratio. In addition, LTD 4 significantly increased the transcription of mtDNA genes. Overexpression of wild-type b-catenin or a constitutively active b-catenin mutant mimicked the effect of LTD 4 on ATP/ADP ratio and mtDNA transcription. These elevations in mitochondrial activity resulted in increased reactive oxygen species levels and subsequent activations of the p65 subunit of NF-kB. CONCLUSIONS: The present novel data show that LTD 4 , presumably through b-catenin accumulation in the mitochondria, affects mitochondrial activity, lending further credence to the idea that inflammatory signalling pathways are intrinsically linked with potential oncogenic signals.

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Cyclooxygenase-2 and prostate carcinogenesis

Cited by 218 publications

References 60 publications

Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

β-Catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells

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