Gemcitabine plus celecoxib (GECO) in advanced pancreatic cancer: a phase II trial

Ferrari, Vittorio; Valcamonico, Francesca; Amoroso, Vito; Simoncini, Edda; Vassalli, Lucia; Marpicati, P.; Rangoni, G.; Grisanti, Salvatore; Tiberio, Guido A M; Nodari, Franco; Strina, Carla; Marini, G

doi:10.1007/s00280-005-0028-1

Cited by 75 publications

(29 citation statements)

References 17 publications

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“…It has a multifunctional role in pancreatic cancer development, being implicated in angiogenesis (for example through upregulation of VEGF), proliferation, invasiveness and immunosuppression. Preclinical studies of COX-2 inhibitors are encouraging 157 -159 , and phase II studies using the selective COX-2 inhibitor celecoxib have yielded promising data 160,161 , although further studies are warranted. Two studies found COX-2 expression to be a prognostic factor independent of conventional clinicopathological parameters 43,44 , but its prognostic significance remains to be confirmed 39,125,153,162 -165 .…”

Section: Cyclo-oxygenasementioning

confidence: 98%

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Ansari

Rosendahl

Elebro

et al. 2011

British Journal of Surgery

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None of the molecular markers described can be recommended for routine clinical use as they were identified in small cohorts and there were inconsistencies between studies. Their prognostic and predictive values need to be validated further in prospective multicentre studies in larger patient populations. A panel of molecular markers may become useful in predicting individual patient outcome and directing novel types of intervention.

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Section: Cyclo-oxygenasementioning

confidence: 98%

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Ansari

Rosendahl

Elebro

et al. 2011

British Journal of Surgery

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“…Recently, anti-COX-2 agents have been documented to have antitumor activity, and some are now being tested as therapies for various cancers [26-29, 31, 35-37] . The antitumor effect of anti-COX-2 agents has also been confirmed in experimental research on pancreatic cancer cells [38][39][40][41] , and clinical investigations have already started [42][43][44] .…”

Section: Discussionmentioning

confidence: 74%

Tumor Size Significantly Correlates with Postoperative Liver Metastases and COX-2 Expression in Patients with Resectable Pancreatic Cancer

et al. 2007

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“…We now know that COX-2 inhibition impacts negatively on cardiac and renal, which causes to serious side effects of prolonged inhibition of this pathway (34). In pancreatic cancer clinical trials, celecoxib in combination with standard chemotherapeutic drugs was found to be modestly effective in some studies but in other studies the effectiveness was limited by toxicity (35)(36)(37)(38)(39). From all of the available data it appears that inhibition of COX-2/PGE2 pathway is effective, but celecoxib does not appear to be the best therapeutic to inhibit this pathway.…”

Section: Discussionmentioning

confidence: 98%

PGE2 regulates pancreatic stellate cell activity via the EP4 receptor

et al. 2013

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Objectives-Pancreatic stellate cells are source of dense fibrotic stroma, a constant pathological feature of chronic pancreatitis (CP) and pancreatic adenocarcinoma (PDAC). We observed correlation between levels of cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE 2 ) and the extent of pancreatic fibrosis. Aim of this study was to delineate the effects of PGE 2 on immortalized human pancreatic stellate cells (HPSC) and to identify the receptor involved. The authors have no any potential conflict of interest including any financial, personal, or other relationships with other people or organizations that could inappropriately influence this work. MethodsPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptPancreas. Author manuscript; available in PMC 2014 April 01. by LC/MS/MS. HPSC proliferation was assessed by MTS assay; migration by Boyden chamber assay and invasion using an invasion chamber. Transient silencing was obtained by siRNA.Results-HPSC express COX-2 and synthesize PGE 2 . PGE 2 stimulated HPSC proliferation, migration and invasion; stimulated expression of both ECM and MMP genes. HPSC expressed all four EP receptors. Only blocking the EP4 receptor resulted in abrogation of PGE 2 mediated HPSC activation. Specificity of EP4 for the effects of PGE 2 on stellate cells was confirmed using specific antagonists.Conclusion-Our data indicate that PGE 2 regulates PSC profibrotic activities via EP4 receptor thus suggesting EP4 receptor as useful therapeutic target for pancreatic cancer to reduce desmoplasia.

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Gemcitabine plus celecoxib (GECO) in advanced pancreatic cancer: a phase II trial

Abstract: GEM in combination with celecoxib showed low toxicity, good clinical benefit rate and good disease control. Further clinical investigation is warranted.

Cited by 75 publications

References 17 publications

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Tumor Size Significantly Correlates with Postoperative Liver Metastases and COX-2 Expression in Patients with Resectable Pancreatic Cancer

PGE2 regulates pancreatic stellate cell activity via the EP4 receptor

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