Enhanced 5-fluorouracil cytotoxicity in high cyclooxygenase-2 expressing colorectal cancer cells and xenografts induced by non-steroidal anti-inflammatory drugs via downregulation of dihydropyrimidine dehydrogenase

Réti, Andrea; Pap, Erna; Adleff, Vilmos; Jeney, A.; Kralovánszky, Judit; Budai, Barna

doi:10.1007/s00280-009-1149-8

“…Some studies have also provided evidence that aspirin promotes deoxyribonucleic acid (DNA) self-healing by the upregulation of hMLH1, hMSH2, hMSH6, hPMS2 [43], and XRCC expression [44], slowing down gene-mutation accumulation, and protecting normal cell DNA [32,45]. Recent studies have suggested several new aspirin pathways, such as inhibiting the synthesis of prostaglandin E2 (PGE2) [46], controlling the number of circulating platelets and their activity levels to evade several innate anti-tumor effects [47][48][49][50], increasing chemo-agent toxicity, and downregulating cellular drug resistance [51,52]. Since the results of these basic studies have mostly been conducted in vitro and have not been proven in humans, these outcomes cannot be presented as definitive mechanisms of aspirin's effects.…”

Section: Discussionmentioning

confidence: 99%

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): study protocol for a multicenter randomized controlled trial

Choi

¹

,

Paik

²

,

You

³

et al. 2020

Trials

2

0

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Background: Endoscopic retrograde biliary drainage (ERBD) is the treatment of choice for patients with malignant distal common bile duct (CBD) obstruction. Self-expandable metal stents (SEMS), which are commonly used in unresectable cases, have many clinical advantages, including longer stent patency. Although the expected patency of SEMS is around 8 months, it has recently been reported that the duration of SEMS' patency in patients using aspirin is prolonged. Our study, therefore, aims to investigate the effect of aspirin on SEMS' patency.Methods/design: This is an investigator-initiated, prospective, multicenter, double-blind, randomized placebocontrolled trial that will be conducted from November 2017 in four tertiary centers in South Korea. We intend to include in our study 184 adult (aged ≥ 20 years) patients with malignant distal CBD obstruction for whom ERBD with SEMS was successfully performed. The patients will be randomly allocated to two groups, which will comprise patients who have either taken 100 mg aspirin or a placebo for 6 months after index ERBD. The primary outcome will be the rate of stent dysfunction, and the secondary outcomes will be the duration of patency, the rate of reintervention, and the occurrence of adverse events. Discussion:The aspirin for metal stents in malignant distal common bile duct obstruction (AIMS) study should determine the efficacy of aspirin in maintaining metal-stent patency in patients with malignant distal CBD obstructive.

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“…[32,45] Recent studies have suggested several new aspirin pathways, such as inhibiting the synthesis of PGE2, [46] controlling the number of circulating platelets and their activity levels to evade several innate anti-tumor effects, [47][48][49][50] increasing chemo agent toxicity, and downregulating cellular drug resistance. [51,52] Since the results of these basic studies have mostly been conducted in vitro and have not been proven in humans, these outcomes cannot be presented as definitive mechanisms of aspirin.…”

Section: Discussionmentioning

confidence: 99%

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): Study protocol for a multicenter randomized controlled trial

Choi

¹

,

Paik

²

,

You

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Background Endoscopic retrograde biliary drainage (ERBD) is the treatment of choice for patients with malignant distal common bile duct (CBD) obstruction. Self-expandable metal stents (SEMS), which are commonly used in unresectable cases, have many clinical advantages, including longer stent patency. Although the expected patency of SEMS is around eight months, it has recently been reported that the duration of SEMS patency in patients using aspirin is prolonged. Our study therefore aims to confirm the effect of aspirin on SEMS patency. Methods This is an investigator-initiated, prospective, multicenter, double-blind, randomized placebo-controlled trial that will be conducted from November 2017 in four tertiary centers in South Korea. We intend to include in our study 184 adult (≥ 20 years) patients with malignant distal CBD obstruction for whom ERBD with SEMS was successfully performed. The patients will be randomly allocated to two groups, which will comprise patients who have either taken 100 mg aspirin or a placebo for six months after index ERBD. The primary outcome will be the rate of stent dysfunction, and the secondary outcomes will be the duration of patency, the rate of reintervention, and the occurrence of adverse events. Discussion The aspirin for metal stents in malignant distal common bile duct obstruction (AIMS) study will determine the efficacy of aspirin in maintaining metal stent patency in patients with malignant distal CBD obstructive.

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“…[29,42] Recent studies have suggested several new aspirin pathways, such as inhibiting the synthesis of PGE2, [43] controlling the number of circulating platelets and their activity levels to evade several innate anti-tumor effects, [44][45][46][47] increasing chemo agent toxicity, and downregulating cellular drug resistance. [48,49] Since the results of these basic studies have mostly been conducted in vitro and have not been proven in humans, these outcomes cannot be presented as definitive mechanisms of aspirin. This study will have some limitations.…”

Section: Discussionmentioning

confidence: 99%

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): Study protocol for a multicenter randomized controlled trial

Choi

¹

,

Paik

²

,

You

³

et al. 2019

Preprint

0

View full text Add to dashboard Cite

Background Endoscopic retrograde biliary drainage (ERBD) is the treatment of choice for patients with malignant distal common bile duct (CBD) obstruction. Self-expandable metal stents (SEMS), which are commonly used in unresectable cases, have many clinical advantages, including longer stent patency. Although the expected patency of SEMS is around eight months, it has recently been reported that the duration of SEMS patency in patients using aspirin is prolonged. Our study therefore aims to confirm the effect of aspirin on SEMS patency. Methods This is an investigator-initiated, prospective, multicenter, double-blind, randomized placebo-controlled trial that will be conducted from November 2017 in four tertiary centers in South Korea. We intend to include in our study 184 adult (≥ 20 years) patients with malignant distal CBD obstruction for whom ERBD with SEMS was successfully performed. The patients will be randomly allocated to two groups, which will comprise patients who have either taken 100 mg aspirin or a placebo for six months after index ERBD. The primary outcome will be the rate of stent dysfunction, and the secondary outcomes will be the duration of patency, the rate of reintervention, and the occurrence of adverse events. Discussion The aspirin for metal stents in malignant distal common bile duct obstruction (AIMS) study will determine the efficacy of aspirin in maintaining metal stent patency in patients with malignant distal CBD obstructive.

show abstract

Enhanced 5-fluorouracil cytotoxicity in high cyclooxygenase-2 expressing colorectal cancer cells and xenografts induced by non-steroidal anti-inflammatory drugs via downregulation of dihydropyrimidine dehydrogenase

Cited by 15 publications

References 39 publications

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): study protocol for a multicenter randomized controlled trial

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): study protocol for a multicenter randomized controlled trial

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): Study protocol for a multicenter randomized controlled trial

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): Study protocol for a multicenter randomized controlled trial

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