Concurrent celecoxib with 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel for stages II – III invasive breast cancer: the OOTR-N001 study

Chow, Louis W C; Tung, Stewart Y.; Ng, Ting Ying; Im, Seock Ah; Lee, Min Hyuk; Yip, Adrian Y S; Toi, Masakazu; Glück, Stefan

doi:10.1517/13543784.2013.766715

Cited by 17 publications

(11 citation statements)

References 28 publications

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“…The inhibitory rates of the 5-FU, high-dose (200 mg/kg) and low-dose (50 mg/kg) celecoxib, and combination of 5-FU with celecoxib groups were 65.8, 49.3, 37.0 and 79.5%, respectively. Furthermore, we found that celecoxib enhanced the antitumor effect of 5-FU, which is consistent with the results of previous studies (27,28). HIF-1α is one of the most important regulatory molecules that respond to hypoxia for cell survival and angiogenesis (29).…”

Section: Discussionsupporting

confidence: 92%

Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H22 murine hepatocarcinoma model

et al. 2014

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Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has recently been shown to affect the development of different types of cancer. The present study utilized a murine H22 hepatocarcinoma model to investigate the molecular mechanisms involved in celecoxib-induced inhibition of tumor angiogenesis. Tumor-bearing mice were randomly divided into five groups: i) control; ii) low-dose celecoxib (50 mg/kg); iii) high-dose celecoxib (200 mg/kg); iv) 5-fluorouracil (5-FU), (20 mg/kg) and v) combination of 5-FU and celecoxib (50 mg/kg). The antitumor effect of celecoxib was determined by measuring tumor volume. Tumor angiogenesis was evaluated by microvessel density (MVD). Tumor histology and immunostaining for CD34 in endothelial cells were performed to detect MVD. The expression levels of phosphatase and tensin homologue deleted from chromosome 10 (PTEN), phosphatidylinositol 3-kinase (PI3K), phospho‑Akt (P-Akt), COX-2, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) were detected by ELISA, immunohistochemistry and western blotting, respectively. We discovered substantial growth delay in murine H22 hepatoma as a result of celecoxib treatment. The inhibition rate of tumor growth induced by high-dose and low-dose celecoxib was 49.3 and 37.0%, respectively (P<0.05). The expression of PI3K, P-Akt, COX-2, HIF-1α, VEGF-A and PTEN in tumor tissues treated with celecoxib was demonstrated by immunohistochemistry, and the MVD was decreased in a dose-dependent manner (P<0.05). Reduced PI3K and P-Akt was particularly apparent in the high-dose celecoxib group (P<0.05). ELISA and western blotting data showed that the expression of PI3K, P-Akt, COX-2, HIF-1α and VEGF-A were reduced and PTEN was increased after treatment with celecoxib. In conclusion, the impact of celecoxib-induced tumor growth delay of murine H22 hepatocarcinoma may correlate with the inhibition of angiogenesis by reducing PI3K, P-Akt, COX-2, HIF-1α and VEGF-A expression and increasing PTEN expression in tumor tissue.

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Section: Discussionsupporting

confidence: 92%

Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H22 murine hepatocarcinoma model

et al. 2014

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“…Indeed it was determined that pharmacological inhibition of COX-2 by Celecoxib led to decreased chemoresistance in preclinical studies [ 44 ]. Currently, multiple clinical trials are underway to investigate the potential of celecoxib as a combinational therapy for the treatment of breast cancer [ 45 – 47 ]. Our data suggests that RhoGDI downregulation could be a critical mechanism of breast cancer progression.…”

Section: Discussionmentioning

confidence: 99%

RhoGDI deficiency induces constitutive activation of Rho GTPases and COX-2 pathways in association with breast cancer progression

et al. 2015

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Rho GDP Dissociation Inhibitor (RhoGDI) is a key regulator of Rho GTPases. Here we report that loss of RhoGDI significantly accelerated xenograft tumor growth of MDA-MB-231 cells in animal models. At the molecular level, RhoGDI depletion resulted in constitutive activation of Rho GTPases, including RhoA, Cdc42, and Rac1. This was accompanied by Rho GTPase translocation from the cytosol to membrane compartments. Notably, COX-2 protein levels, mRNA expression, and biological activity were markedly increased in RhoGDI-deficient cells. The upregulated expression of COX-2 was directly associated with increased Rho GTPase activity. Further, we assessed the expression level of RhoGDI protein in breast tumor specimens (n = 165) by immunohistochemistry. We found that RhoGDI expression is higher in the early stages of breast cancer followed by a significant decrease in malignant tumors and metastatic lesions (p 0.01). These data suggest that downregulation of RhoGDI could be a critical mechanism of breast tumor development, which may involve the hyperactivation of Rho GTPases and upregulation of COX-2 activity. Additional studies are warranted to evaluate the therapeutic potential of inhibiting Rho GTPases and COX-2 for treating breast cancers.

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“…A study containing 50 patients showed that preoperative FEC with celecoxib (FECC) could provide lower intensity staining for COX-2, Ki-67, and p53 in 90% patients, while no difference was observed on tumor size, grade, or axillary lymph node status. 104 In a Phase II, multicenter, open-label, single-arm study (N001), 105 64 invasive BC patients received four cycles of FEC (500, 100, 500 mg/m 2 ) followed by four cycles of docetaxel (100 mg/m 2 ) with celecoxib (200 mg twice daily) as neoadjuvant therapy (NAT). After NAT, 43 patients achieved clinical complete response (cCR) and 13 achieved clinical partial response (cPR).…”

Section: Integrating Celecoxib Into Bc Treatmentmentioning

confidence: 99%

Celecoxib in breast cancer prevention and therapy

Hao

Cao

et al. 2018

CMAR

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Breast cancer has a high incidence worldwide. The results of substantial studis reveal that inflammation plays an important role in the initiation, development, and aggressiveness of many malignancies. The use of celecoxib, a novel NSAID, is repetitively associated with the reduced risk of the occurrence and progression of a number of types of cancer, particularly breast cancer. This observation is also substantiated by various meta-analyses. Clinical trials have been implemented on integration treatment of celecoxib and shown encouraging results. Celecoxib could be treated as a potential candidate for antitumor agent. There are, nonetheless, some unaddressed questions concerning the precise mechanism underlying the anticancer effect of celecoxib as well as its activity against different types of cancer. In this review, we discuss different mechanisms of anticancer effect of celecoxib as well as preclinical/clinical results signifying this beneficial effect.

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Concurrent celecoxib with 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel for stages II – III invasive breast cancer: the OOTR-N001 study

Cited by 17 publications

References 28 publications

Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H22 murine hepatocarcinoma model

Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H22 murine hepatocarcinoma model

RhoGDI deficiency induces constitutive activation of Rho GTPases and COX-2 pathways in association with breast cancer progression

Celecoxib in breast cancer prevention and therapy

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