A randomized double-blind placebo-controlled phase II trial of the cyclooxygenase-2 inhibitor Celecoxib in the treatment of cervical dysplasia

Farley, John H.; Truong, Vu; Goo, Elwin D.H.; Uyehara, Catherine F. T.; Belnap, Christina; Larsen, Wilma

doi:10.1016/j.ygyno.2006.03.036

Cited by 32 publications

(23 citation statements)

References 22 publications

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“…These findings led to the accelerated FDA approval of celecoxib for adjuvant therapy in the treatment of familial adenomatous polyposis in 1999 (42). Studies have also indicated that celecoxib may have activity against other cancers, such as ovarian cancer, as well (43). However, the use of celecoxib and other NSAIDs for cancer prevention and therapy remains controversial, with many clinical studies indicating that the compounds do not have significant beneficial effects for patients.…”

Section: Current Status Of Anti-inflammatory Agents For Cancermentioning

confidence: 99%

Anti-Inflammatory Agents for Cancer Therapy

Rayburn

Ezell²,

Zhang³

2009

Mol Cell Pharmacol

295

219

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Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents.

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Section: Current Status Of Anti-inflammatory Agents For Cancermentioning

confidence: 99%

Anti-Inflammatory Agents for Cancer Therapy

Rayburn

Ezell²,

Zhang³

2009

Mol Cell Pharmacol

295

219

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“…Selective COX-2 inhibitors are used in treatment of colorectal polyps (57) and in women with high grade cervical dysplasia (58). Furthermore, experimental studies have shown that the inhibition of COX-2 or PGE2 leads to in vivo tumor reduction in murine lung cancer models (59).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cyclooxygenase-2 Down-regulates Aromatase Activity and Decreases Proliferation of Leydig Tumor Cells

Sirianni

Chimento

Luca

et al. 2009

Journal of Biological Chemistry

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Our recent studies have revealed that estrogens stimulate an autocrine mechanism determining Leydig tumor cell proliferation. Estrogen overproduction is due to an elevated steroidogenic factor-1 (SF-1) expression and cAMP-response element-binding protein (CREB) phosphorylation, both inducing aromatase overexpression. Although we have shown that increased SF-1 expression depends mainly on higher local insulin-like growth factor I production, the mechanisms and factors determining increased CREB activation in Leydig tumor cells are not completely understood. In this study, we investigated the role of cyclooxygenase-2 (COX-2) in CREB dependent-aromatase expression in Leydig tumor cells. We found that COX-2 is expressed in rat and human Leydigiomas as well as in the rat Leydig tumor cell line R2C, but not in normal testis. Our data indicate that in R2C cells the COX-2-derived prostaglandin E2 (PGE2) binds the PGE2 receptor EP4 and activates protein kinase A (PKA) and ultimately CREB. Inhibitors for COX-2 (NS398), EP4 (AH23848), and PKA (H89) decreased aromatase expression and activity as a consequence of a decreased phosphorylated CREB recruitment to the PII promoter of the aromatase gene. The COX-2/PGE2/PKA pathway also seems to be involved in aromatase post-translational activation, an observation that requires further studies. The reduction in aromatase activity was responsible for a drop in estrogen production and subsequent reduction in cyclin E expression resulting in a decrease in tumor Leydig cell proliferation. Furthermore, COX-2 silencing caused a significant decrease in CREB phosphorylation, aromatase expression, and R2C cell proliferation. These novel findings clarify the mechanisms involved in the growth of Leydig cell tumors and should be taken into account in determining new therapeutic approaches.

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“…58,59 Based on these promising data, the use of Hsp-based immunotherapy was extended to CIN II, III. Because it is the most common HPV type among women with CIN II, III, Hsp used for such lesions was fused with the E7 oncoprotein of HPV 16 (HspE7 HPV 16). The overall response rates in these preliminary studies ranged from 40% to 78%, in which 22% to 55% had a complete response.…”

Section: Heat Shock Fusion Protein-based Immunotherapymentioning

confidence: 99%

“…14,15 Encouraged by this favorable result, gynecologists extended the use of COX-2 inhibitors for treating CIN II, III. Farley et al 16 evaluated the effi cacy of the COX-2 inhibitor celecoxib in the regression of histologically proven CIN II, III, in a prospective randomized double-blind placebocontrolled phase II study in 25 women. Patients who enrolled in this study were prescribed celecoxib at 200 mg twice a day (n = 12) or a placebo (n = 13).…”

Section: Introductionmentioning

confidence: 99%

“…However, it should be noted that in these aforementioned trials, 18,19 either the prescribed dosage or the duration of the administered COX-2 inhibitor was obviously higher and longer than that used in the CIN II, III studies, so the results may be viewed with caution. 16,17 These higher doses or longer durations possibly pose a much higher risk of adverse events. If a safe low-dose and short-course administration of COX-2 inhibitor, as per phase II protocol, is ascertained, a randomized phase III trial is warranted to validate the effectiveness of a COX-2 inhibitor in the treatment of CIN II, III.…”

Section: Introductionmentioning

confidence: 99%

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Medical treatment of cervical intraepithelial neoplasia II, III: an update review

Kietpeerakool

Srisomboon

2009

Int J Clin Oncol

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Cervical intraepithelial neoplasia (CIN) II, III is a preinvasive stage of squamous cell carcinoma of the uterine cervix. The standard treatment for CIN II, III consists of ablation and excision. However, nonsurgical treatment may be necessary for some women to preserve future reproductive potential. This review was conducted to summarize available published data on the efficacy and safety of medical treatment for CIN II, III. Based on existing studies, cyclooxygenase (COX)-2 inhibitors; indole-3-carbinol; and novel immunotherapy agents, including ZYC101a, MVA E2, and HspE7, have been observed as possessing therapeutic activity without any major treatment-related complications. These promising results provide important data for the future direction of clinical research.

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A randomized double-blind placebo-controlled phase II trial of the cyclooxygenase-2 inhibitor Celecoxib in the treatment of cervical dysplasia

Cited by 32 publications

References 22 publications

Anti-Inflammatory Agents for Cancer Therapy

Anti-Inflammatory Agents for Cancer Therapy

Inhibition of Cyclooxygenase-2 Down-regulates Aromatase Activity and Decreases Proliferation of Leydig Tumor Cells

Medical treatment of cervical intraepithelial neoplasia II, III: an update review

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