A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer: a phase II trial

Jakobsen, Anders; Mortensen, John Pløen; Bisgaard, Christer Z.; Lindebjerg, Jan; Rafaelsen, Søren Rafael; Bendtsen, Vagn Ove

doi:10.1007/s00384-007-0407-7

Cited by 25 publications

(20 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There has been a significant interest in COX-2 and its role in the development and progression of cancer over the past number of years, with a number of clinical trials examining selective COX-2 inhibition as a potential therapeutic strategy [10][11][12][13]. COX-2 expression has been associated with a poor prognosis in a variety of cancer states [14][15][16].…”

mentioning

confidence: 99%

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer

Cathcart

Reynolds

O’Byrne

et al. 2010

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

Prostacyclin synthase and thromboxane synthase signaling via arachidonic acid metabolism affects a number of tumor cell survival pathways such as cell proliferation, apoptosis, tumor cell invasion and metastasis, and angiogenesis. However, the effects of these respective synthases differ considerably with respect to the pathways described.While prostacyclin synthase is generally believed to be pro-tumor, an anti-carcinogenic role for thromboxane synthase has been demonstrated in a variety of cancers. The balance of oppositely acting COX-derived prostanoids influences many processes throughout the body, such as blood pressure regulation, clotting, and inflammation. The PGI 2 /TXA 2 ratio is of particular interest in-vivo, with the corresponding synthases shown to be differentially regulated in a variety of disease states. Pharmacological inhibition of thromboxane synthase has been shown to significantly inhibit tumor cell growth, invasion, metastasis and angiogenesis in a range of experimental models. In direct contrast, prostacyclin synthase over-expression has been shown to be chemopreventative in a murine model of the disease, suggesting that the expression and activity of this enzyme may protect against tumor development.In this review, we discuss the aberrant expression and known functions of both prostacyclin synthase and thromboxane synthase in cancer. We discuss the effects of these enzymes on a range of tumor cell survival pathways, such as tumor cell proliferation, induction of apoptosis, invasion and metastasis, and tumor cell angiogenesis. As downstream signaling pathways of these enzymes have also been implicated in cancer states, we examine the role of downstream effectors of PGIS and TXS activity in tumor A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTProstacyclin Synthase, Thromboxane Synthase and Cancer 4 growth and progression. Finally, we discuss current therapeutic strategies aimed at targeting these enzymes for the prevention/treatment of cancer. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTProstacyclin Synthase, Thromboxane Synthase and Cancer 5 IntroductionCancer causes seven million deaths annually, accounting for 12.5% of deaths worldwide. It is the second leading cause of death in the developed world and is among the three leading causes of death for adults in developed countries. It is estimated that, by 2020there will be 16 million new cases every year, representing a 50% increase in cancer incidence [1].The arachidonic acid pathway is responsible for the generation of a wide variety of bioactive metabolites. These metabolites, otherwise known as eicosanoids, have beenshown to be involved in many different pathologies, including inflammation and cancer [2].Arachidonic acid can be metabolised into the biologically active eicosanoids via the action of three separate groups of enzymes: cyclooxygenases (COX), lipoxygenases (LOX), and epoxygenases (cyctochrome P450). The COX enzymes catalyse the first step in the synthesis of prostanoids from arachidonic acid [3]. ...

show abstract

mentioning

confidence: 99%

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer

Cathcart

Reynolds

O’Byrne

et al. 2010

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

show abstract

“…The test cohort included 65 patients who were treated according to two previously published studies (22,23) with long-course CRT between 2002 and 2005, comprising conventional radiotherapy of 60 Gy/30 fractions and supplemented by a brachytherapy boost of 5 Gy. Concomitant chemotherapy consisting of 300 mg/m 2 UFT (uracil-tegafur; molar ratio 4:1) and 22.5 mg isovorin was administered to patients on treatment days.…”

Section: Methodsmentioning

confidence: 99%

“…Concomitant chemotherapy was administered as previously described (24) Patient consent was obtained prior to inclusion in the studies (22)(23)(24) which were approved by the local ethics committee of The Regional Scientific Ethical Committee for Southern Denmark.…”

Section: Methodsmentioning

confidence: 99%

Single nucleotide polymorphisms in the HIF-1α gene and chemoradiotherapy of locally advanced rectal cancer

et al. 2012

Self Cite

View full text Add to dashboard Cite

“…• Celecoxib: This selective cyclooxygenase-2 inhibitor, which influences the prostaglandin synthesis, induced rash in 50% of LARC patients, and the trial thus was terminated (194).…”

Section: New Crt Regimensmentioning

confidence: 99%

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

Folkvord

Flatmark

Seierstad

et al. 2008

Radiotherapy and Oncology

View full text Add to dashboard Cite

A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer: a phase II trial

Abstract: The addition of a COX-2 inhibitor to chemotherapy-enhanced radiation treatment of rectal cancer was not feasible due to a high incidence of rash in the present study.

Cited by 25 publications

References 13 publications

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer

Single nucleotide polymorphisms in the HIF-1α gene and chemoradiotherapy of locally advanced rectal cancer

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

Contact Info

Product

Resources

About