Regression of endometrial explants in rats treated with the cyclooxygenase-2 inhibitor rofecoxib

Dogan, Erbil; Saygılı, Uğur; Posacı, Cemal; Tuna, Burçin; Caliskan, Sezer; Altunyurt, Sabahattin; Saatli, Bahadır

doi:10.1016/j.fertnstert.2004.06.033

Cited by 77 publications

(41 citation statements)

References 36 publications

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“…Our group has demonstrated that selective inhibition of COX-2 activity with celecoxib reduces the proliferation rate of endometrial epithelial cells as well as it augments their apoptosis levels both in vitro and in vivo (Olivares et al 2008. Similar results were obtained by other investigators demonstrating that the inhibition of COX-2 activity has antiproliferative, proapoptotic, and antiangiogenic effects in several in vivo and in vitro cancer models (Gupta et al 2004, Basu et al 2005, Dandekar et al 2005, Barnes et al 2007 and in other models of endometriosis (Dogan et al 2004, Laschke et al 2007, Machado et al 2010. Moreover, a COX-2 inhibitor has been used in a pilot study evaluating pain response in endometriosis patients with good results (Cobellis et al 2004).…”

Section: Introductionsupporting

confidence: 84%

Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

et al. 2013

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Endometriosis is a benign gynecological disease. Cyclooxygenase-2 (COX-2) and aromatase proteins have been shown to be overexpressed in eutopic endometrium from women suffering from this disease compared to disease-free women. Furthermore, inhibition of these molecules individually was demonstrated to have antiproliferative and proapoptotic effects both in vitro and in vivo in several models. In this study, the effect of combining celecoxib, a selective COX-2 inhibitor, and anastrozole, an aromatase inhibitor, on the implantation and growth of endometriotic like lesions in a murine model of endometriosis was evaluated. Endometriosis was surgically induced in female BALB/c mice. After 28 days of treatment with celecoxib, anastrozole, or their combination, animals were killed and lesions were counted, measured, excised, and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for assessment of cell proliferation and vascularization. TUNEL technique was performed for apoptosis evaluation. Celecoxib was the only treatment to significantly reduce the number of lesions established per mouse, their size and vascularized area. In addition, cell proliferation was significantly diminished and apoptosis was significantly enhanced by both individual treatments. When the therapies were combined, they reversed their effects. These results confirm that celecoxib and anastrozole separately decrease endometriotic growth, but when combined they might have antagonizing effects.

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Section: Introductionsupporting

confidence: 84%

Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

et al. 2013

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“…The mostly used drugs currently are medroxiprogesterone acetate, danazol, oral contraceptives and GnRH analogues. They bring good results in pain events, but they interfere in fertility, and the treatment cease is followed by endometriosis recurrency 8 . Several drugs have been researched in experimental studies as endometriosis optional therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the macroscopic growth degree of experimental endometriosis in rats

et al. 2007

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PURPOSE: To evaluate macroscopically the growth degree of self-transplantation of endometriosis in rats. METHODS: Forty female rats, after a 7-day period for adpating and evaluating of the estrous cycle regularity, underwent tail abdominal midline laparotomy with 3-cm cuts. The average third of the left uterine horn was removed, 4mm x 4mm patches in liquid environment were made, and self-transplanted in the rat mesenterium with a single stitch, and the endometrial surface of the endometriotic implant facing the lumen of the peritoneal cavity. The rats were programmed to die after three weeks. The abdominal cavity displaying was held and self-transplants were identified and classified. RESULTS: The results achieved were: one case for degree 0 (2,5%), three cases for degree 1 (7,5%), eleven cases for degree II (27,5%) and twenty-five cases for degree III (62,5%). CONCLUSION: The experimental endometriosis development, through the self-transplantation technique, showed to be most common in degrees 3 and 2 of development.

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“…During the last few years, COX-2 inhibitors have been evaluated in the context of endometriosis in animal (rodent) studies (Dogan et al, 2004;Matsuzaki et al, 2004;Ozawa et al, 2006;Laschke et al, 2007). Their effectiveness was also assessed in endometriosis patients (Cobellis et al, 2004), although very little is known about the mechanism of such inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis

et al. 2009

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background: Increased peritoneal eicosanoid concentrations have been reported in endometriosis patients and might be important in disease-associated pain and inflammation. Here, we evaluated the expression of key biosynthetic and catabolic enzymes involved in this abnormal eicosanoid production in peritoneal macrophages and endometriotic lesions.methods: Peritoneal macrophages, endometriotic lesions and matched eutopic endometrium were collected from endometriosis patients (n ¼ 40). Peritoneal macrophages and eutopic endometrium samples were also collected from disease-free women (n ¼ 25). Expression of type IIA secretory phospholipase A 2 (sPLA 2 -IIA), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 5-lipoxygenase (5-LO) was quantified by real-time PCR, and these five key enzymes were localized by immunohistochemistry.results: sPLA 2 -IIA, COX-2 and mPGES-1 mRNA was significantly increased in peritoneal macrophages of endometriosis patients compared with controls (P ¼ 0.006, P ¼ 0.016 and P ¼ 0.025, respectively). In endometriosis patients, sPLA 2 -IIA, mPGES-1 and 15-PGDH mRNA was significantly enhanced in peritoneal lesions compared with matched eutopic endometrium (P , 0.001, P , 0.001 and P ¼ 0.005, respectively). In eutopic endometrium, a significant decrease in 15-PGDH mRNA was found in the endometriosis group compared with controls (P ¼ 0.023). Finally, sPLA 2 -IIA, COX-2, mPGES-1 and 15-PGDH immunostaining was found mainly in endometrial glands, whereas 5-LO was distributed throughout the glands and stroma. conclusions: Our study highlights an imbalance between eicosanoid biosynthesis and degradation in endometriosis patients. Both peritoneal macrophages and endometriotic lesions may be involved. Research into new molecules inhibiting biosynthetic enzymes (such as sPLA 2 -IIA and mPGES-1) and/or activating catabolic enzymes (such as 15-PGDH) may prove to be a major field of investigation in the development of targeted medical therapies.

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Regression of endometrial explants in rats treated with the cyclooxygenase-2 inhibitor rofecoxib

Cited by 77 publications

References 36 publications

Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

Evaluation of the macroscopic growth degree of experimental endometriosis in rats

Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis

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