Q3137448 (Q3137448): Difference between revisions
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(Created claim: summary (P836): Acetyl salicylic acid (ASA) seems to be the ideal candidate for colorectal cancer chemoprevention (CCR). Several ongoing trials also aim to evaluate the effect of ASA as cotherapy after diagnosis. The mechanisms of action, the appropriate dose and the ideal target population are unknown. We have shown that doses of 100 mg of ASA induce direct, partial but persistent acetylation of COX-1 in the normal colorectal mucosa. The primary objective is...) |
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Acetyl salicylic acid (ASA) seems to be the ideal candidate for colorectal cancer chemoprevention (CCR). Several ongoing trials also aim to evaluate the effect of ASA as cotherapy after diagnosis. The mechanisms of action, the appropriate dose and the ideal target population are unknown. We have shown that doses of 100 mg of ASA induce direct, partial but persistent acetylation of COX-1 in the normal colorectal mucosa. The primary objective is to evaluate through a proteomic trial the direct effect of different doses of ASA on COX-1 and COX-2 on platelets, healthy colonic tissue and tumor as clinically effective biomarkers. As secondary objectives: evaluate the effect of ASA on PGE2 and p-S6 levels in the CRC mucosa, the effect on indirect biomarkers of its action at systemic level (TXB2, PFA and urinary levels of 11-dehydro-TXB2 (TX-M) and systemic biomarkers of inflammatory/tumorigenic COX-2 activity (PGE-M). Methods: Randomised Phase IV clinical trial in patients with newly diagnosed RCC. 60 patients will be evaluated in 3 groups of 20, who will receive 100 or 300 mg/day or 100 mg/12 hours of enteric-coated ASA for 3± 1 week, prior to definitive treatment by surgery. The acetylation of COX-1 and COX-2 is determined. Eicosanoid levels in target organs. Expected results: Evidence of the current uncertainty about the mechanism of action and the dose(s) required to obtain the best chemopreventive effect with ASA in CRC. Confirm the acetylation of COX as an efficacy biomarker with AAS. (English) | |||||||||||||||
| Property / summary: Acetyl salicylic acid (ASA) seems to be the ideal candidate for colorectal cancer chemoprevention (CCR). Several ongoing trials also aim to evaluate the effect of ASA as cotherapy after diagnosis. The mechanisms of action, the appropriate dose and the ideal target population are unknown. We have shown that doses of 100 mg of ASA induce direct, partial but persistent acetylation of COX-1 in the normal colorectal mucosa. The primary objective is to evaluate through a proteomic trial the direct effect of different doses of ASA on COX-1 and COX-2 on platelets, healthy colonic tissue and tumor as clinically effective biomarkers. As secondary objectives: evaluate the effect of ASA on PGE2 and p-S6 levels in the CRC mucosa, the effect on indirect biomarkers of its action at systemic level (TXB2, PFA and urinary levels of 11-dehydro-TXB2 (TX-M) and systemic biomarkers of inflammatory/tumorigenic COX-2 activity (PGE-M). Methods: Randomised Phase IV clinical trial in patients with newly diagnosed RCC. 60 patients will be evaluated in 3 groups of 20, who will receive 100 or 300 mg/day or 100 mg/12 hours of enteric-coated ASA for 3± 1 week, prior to definitive treatment by surgery. The acetylation of COX-1 and COX-2 is determined. Eicosanoid levels in target organs. Expected results: Evidence of the current uncertainty about the mechanism of action and the dose(s) required to obtain the best chemopreventive effect with ASA in CRC. Confirm the acetylation of COX as an efficacy biomarker with AAS. (English) / rank | |||||||||||||||
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| Property / summary: Acetyl salicylic acid (ASA) seems to be the ideal candidate for colorectal cancer chemoprevention (CCR). Several ongoing trials also aim to evaluate the effect of ASA as cotherapy after diagnosis. The mechanisms of action, the appropriate dose and the ideal target population are unknown. We have shown that doses of 100 mg of ASA induce direct, partial but persistent acetylation of COX-1 in the normal colorectal mucosa. The primary objective is to evaluate through a proteomic trial the direct effect of different doses of ASA on COX-1 and COX-2 on platelets, healthy colonic tissue and tumor as clinically effective biomarkers. As secondary objectives: evaluate the effect of ASA on PGE2 and p-S6 levels in the CRC mucosa, the effect on indirect biomarkers of its action at systemic level (TXB2, PFA and urinary levels of 11-dehydro-TXB2 (TX-M) and systemic biomarkers of inflammatory/tumorigenic COX-2 activity (PGE-M). Methods: Randomised Phase IV clinical trial in patients with newly diagnosed RCC. 60 patients will be evaluated in 3 groups of 20, who will receive 100 or 300 mg/day or 100 mg/12 hours of enteric-coated ASA for 3± 1 week, prior to definitive treatment by surgery. The acetylation of COX-1 and COX-2 is determined. Eicosanoid levels in target organs. Expected results: Evidence of the current uncertainty about the mechanism of action and the dose(s) required to obtain the best chemopreventive effect with ASA in CRC. Confirm the acetylation of COX as an efficacy biomarker with AAS. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 12:34, 12 October 2021
Project Q3137448 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3137448 in Spain |
Statements
70,000.0 Euro
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140,000.0 Euro
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50.0 percent
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1 January 2018
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31 March 2021
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INSTITUTO DE INVESTIGACION SANITARIA ARAGON
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41°39'7.67"N, 0°52'51.38"W
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50297
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El ácido acetíl salicílico (AAS) parece el candidato ideal en quimioprevención de cáncer colorectal (CCR). Varios ensayos en marcha pretenden evaluar también el efecto del AAS como coterapia tras el diagnóstico. Se desconocen los mecanismos de acción, la dosis apropiada y la población diana ideal. Hemos demostrado que dosis de 100 mg de AAS inducen acetilación directa, parcial, pero persistente, de la COX-1 en la mucosa colorectal normal. El objetivo primario es evaluar mediante un ensayo proteómico el efecto directo de dosis diferentes de AAS sobre la COX-1 y COX-2 en plaquetas, tejido colónico sano y tumoral como biomarcadores de eficacia clínica. Como objetivos secundarios: evaluar el efecto del AAS en los niveles de PGE2 y p-S6 en la mucosa del CCR, el efecto sobre biomarcadores indirectos de su acción a nivel sistémico, (TXB2, PFA y niveles urinarios de 11-dehidro-TXB2 (TX-M) y biomarcadores sistémicos de actividad de COX-2 inflamatoria/tumorigénica (PGE-M). Métodos: Ensayo clínico aleatorizado en fase IV en pacientes con CCR de reciente diagnóstico. Se evaluaran 60 pacientes en 3 grupos de 20, que recibirán 100 o 300 mg/día o 100 mg/12 horas de AAS con cubierta entérica durante 3±1 semana, previo al tratamiento definitivo mediante cirugía. Se determina la acetilación de COX-1 y COX-2. Niveles de eicosanoides en órganos diana. Resultados esperados: Evidencias a la incertidumbre actual sobre los mecanismo de acción y la/s dosis requeridas para obtener el mejor efecto quimiopreventivo con AAS en el CCR. Confirmar la acetilación de COX como biomarcador de eficacia con AAS. (Spanish)
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Acetyl salicylic acid (ASA) seems to be the ideal candidate for colorectal cancer chemoprevention (CCR). Several ongoing trials also aim to evaluate the effect of ASA as cotherapy after diagnosis. The mechanisms of action, the appropriate dose and the ideal target population are unknown. We have shown that doses of 100 mg of ASA induce direct, partial but persistent acetylation of COX-1 in the normal colorectal mucosa. The primary objective is to evaluate through a proteomic trial the direct effect of different doses of ASA on COX-1 and COX-2 on platelets, healthy colonic tissue and tumor as clinically effective biomarkers. As secondary objectives: evaluate the effect of ASA on PGE2 and p-S6 levels in the CRC mucosa, the effect on indirect biomarkers of its action at systemic level (TXB2, PFA and urinary levels of 11-dehydro-TXB2 (TX-M) and systemic biomarkers of inflammatory/tumorigenic COX-2 activity (PGE-M). Methods: Randomised Phase IV clinical trial in patients with newly diagnosed RCC. 60 patients will be evaluated in 3 groups of 20, who will receive 100 or 300 mg/day or 100 mg/12 hours of enteric-coated ASA for 3± 1 week, prior to definitive treatment by surgery. The acetylation of COX-1 and COX-2 is determined. Eicosanoid levels in target organs. Expected results: Evidence of the current uncertainty about the mechanism of action and the dose(s) required to obtain the best chemopreventive effect with ASA in CRC. Confirm the acetylation of COX as an efficacy biomarker with AAS. (English)
12 October 2021
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Zaragoza
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Identifiers
PI17_01109
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