Cyclooxygenase-2 expression in endometrial cancer: Correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase

Fujiwaki, Ritsuto; Iida, Kohji; Kanasaki, Haruhiko; Ozaki, Tomoya; Hata, Kohkichi; Miyazaki, Kohji

doi:10.1053/hupa.2002.31292

Cited by 112 publications

(77 citation statements)

References 26 publications

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“…[12][13][14] To account for the fact that tumor-produced COX-2 might be an immunosuppressive effector, there are several possible explanations.…”

Section: Discussionmentioning

confidence: 99%

“…Among several possibilities, cyclooxygenase (COX) has received much attention recently for immunosuppression of antitumor immunity, as well as inflammation, carcinogenesis, 7,8 apoptosis, 9,10 metastasis, 11 angiogenesis [12][13][14] and poor prognosis. [15][16][17] Recent studies of in vitro or animal models have revealed that COX-2 may be a critical factor in enabling carcinoma cells to escape host immune defenses by modulation of cytokine production, 18 dysfunction of dendritic cells 19 and suppression of lymphocyte proliferation.…”

mentioning

confidence: 99%

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Role of cyclooxygenase‐2 in immunomodulation and prognosis of endometrial carcinoma

Ohno

Suzuki

et al. 2005

Intl Journal of Cancer

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Although there are several hypotheses explaining the mechanisms of immune-privileged status of malignant tumor, the exact pathway has yet to be explored. Cyclooxygenase (COX)-2 plays a vital role in prognosis of cancer patients in terms of contribution to neoangiogenesis and apoptosis inhibition; however, the impact of COX-2 in immunomodulation has not been reported. We have evaluated the expression of COX-2 and its impact on infiltration of immune-competent cells into the tumor cell nest in endometrial carcinoma. Tissue specimens from 70 endometrial carcinoma patients who had undergone a curative resection were evaluated for COX-2 expression and host immune status (CD8 ؉ T cells). COX-2 expression was associated with FIGO stage and myometrial invasion, but there was no statistically significant impact. CD8 ؉ T cells within cancer cell nest (Nest CD8) were inversely correlated with the expression level of COX-2 (p ‫؍‬ 0.0006). Nest CD8 became an independent predictor of patient survival (Hazard ratio ‫؍‬ 10.300, p ‫؍‬ 0.0304) in Cox's multivariate analysis. The expression level of COX-2 was found to be a significant predictor of disease relapse in univariate analysis (p ‫؍‬ 0.0294) but not in multivariate analysis (p ‫؍‬ 0.5949). In conclusion, increased nest CD8 produced a survival advantage in endometrial carcinoma patients. Moreover, tumor-produced COX-2, which reduces the infiltration of CD8 ؉ T cells into cancer cell nests, may allow tumors to avoid immune surveillance.

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“…[12][13][14] To account for the fact that tumor-produced COX-2 might be an immunosuppressive effector, there are several possible explanations.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Role of cyclooxygenase‐2 in immunomodulation and prognosis of endometrial carcinoma

Ohno

Suzuki

et al. 2005

Intl Journal of Cancer

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“…Recently, it has been reported that COX-2 works on angiogenesis associated with tumor growth and advancement in the following tumors: advanced ovarian serous carcinomas [21], uterine endometrial cancers [22], breast cancers [23], gastric cancers [24], renal cell carcinomas [25], head and neck squamous cell carcinoma [26] and colon cancers [27]. Colon cancer cell line HCA-7 cells overexpress COX-2 and co-express VEGF, bFGF, transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) [27].…”

Section: Introductionmentioning

confidence: 99%

Expression of cyclooxygenase-2 related to angiogenesis in uterine cervical cancers

et al. 2006

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“…The scoring methods were modified by Fujiwaki et al (26). Namely, the percentage of COX-1 and -2 immunostaining in the glandular and stromal cells were graded as follows: 0, no staining; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%.…”

Section: Immunohistochemical Expression Of Cox-1/2 Il-1· and Tnf-· Pmentioning

confidence: 99%

“…ranged from 0 to 12 (26). The immunohistochemical findings were analyzed by two independent investigators counting >200 cells and discordant results were reviewed jointly.…”

Section: Immunohistochemical Expression Of Cox-1/2 Il-1· and Tnf-· Pmentioning

confidence: 99%

Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice

Niwa

Zhou²,

Onogi³

et al. 2007

Oncol Rep

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Abstract. We have previously reported on the inhibitory effect of Glycyrrhizae radix (Gl radix) on mouse endometrial carcinogenesis. The present study was performed to clarify the effects of Gl radix and glycyrrhizin (GL), the main part of Gl radix, on estradiol (E 2 )-related endometrial carcinogenesis. Both Gl radix and GL exerted a significant decrease in the COX-2, IL-1· and TNF-· mRNA expressions. GL generated a significant decrease in the incidence of endometrial adenocarcinoma. Accordingly, the preventive effects of Gl radix may be attributable to GL, thus being related with the suppression of COX-2, IL-1· and TNF-·. Gl radix and GL could therefore be a promising formula for the chemoprevention of human endometrial cancer. IntroductionGlycyrrhizin (GL), a major constituent of Glycyrrhizae radix (Gl radix) which is ~10% of the dry weight of Gl radix extract, is the calcium and potassium salt of glycyrrhizinic acid. GL glycoside loses its sweet taste and upon hydrolysis is then converted to aglycone glycyrrhetinic acid plus two molecules of glucuronic acid. GL has an anti-estrogenic as well as an estrogenic effect (1). There is some evidence that GL has a protective effect on the skin (2,3) or liver carcinogenesis (4,5).It is known that Gl radix is widely used as a Kampo medicine in Asian countries and ~75% of traditional Japanese and Chinese medicines contain this agent. We have previously reported that Gl radix has a preventive effect on endometrial carcinogenesis in mice, and this effect is related to the inhibition of the expression of estrogen-stimulated genes c-fos/jun mRNA and proteins (6). We also proved that the herbal complex containing Gl radix suppresses cell proliferation in a chemo-endocrine resistant cancer cell line (7). In general, the anti-estrogenic effects are considered to have a protective effect against the occurrence of estrogendependent cancers. Such effects are confirmed in animal models of uterine endometrial cancer (8).Cyclooxygenase (COX), an enzyme that activates the production of prostaglandins from arachidonic acid, has two isoforms. COX-2 has attracted considerable attention in connextion with carcinogenesis in organs such as the large bowel, mammary glands and breast carcinogenesis (9-11). There is evidence that the COX activity is related to the promotion and progression in the tumorigenesis of the prostatic gland, stomach and lung (12)(13)(14). It remains unclear whether COX-2 is involved in E 2 related mouse endometrial carcinogenesis, although a high expression level of COX-2 has been confirmed in human endometrial carcinomas (15). In this study, we examined the possible association of the preventive effects of GL on E 2 -induced mouse endometrial carcinogenesis with COX-2 activity.We have reported that the expression of internal cytokines, interleukin (IL)-1· and tumor necrosis factor (TNF)-·, increase after E 2 treatment (16). Such an increase of the internal cytokines is suggested to contribute to both tumor promotion and progression (17)(18)(19). Such circumstances ...

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Cyclooxygenase-2 expression in endometrial cancer: Correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase

Cited by 112 publications

References 26 publications

Role of cyclooxygenase‐2 in immunomodulation and prognosis of endometrial carcinoma

Role of cyclooxygenase‐2 in immunomodulation and prognosis of endometrial carcinoma

Expression of cyclooxygenase-2 related to angiogenesis in uterine cervical cancers

Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice

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