welcome to oneFAPvoice
- a positively charged Familial Adenomatous Polyposis community.- join today!
- login
Effects of Celecoxib on Prostanoid Biosynthesis and Circulating Angiogenesis Proteins in Familial Adenomatous Polyposis
source: The Journal of pharmacology and experimental therapeutics
year: 2012
authors: Dovizio M, Tacconelli S, Ricciotti E, Bruno A, Maier T J, Anzellotti P, Di Francesco L, Sala P, Signoroni S, Bertario L, Dixon D A, Lawson J A, Steinhilber D, FitzGerald G A, Patrignani P
summary/abstract:Vascular cyclooxygenase (COX)-2-dependent prostacyclin (PGI(2)) may affect angiogenesis by preventing endothelial activation and platelet release of angiogenic factors present in platelet α-granules. Thus, a profound inhibition of COX-2-dependent PGI(2) might be associated with changes in circulating markers of angiogenesis. We aimed to address this issue by performing a clinical study with celecoxib in familial adenomatous polyposis (FAP). In nine patients with FAP and healthy controls, pair-matched for gender and age, we compared systemic biosynthesis of PGI(2), thromboxane (TX) A(2), and prostaglandin (PG) E(2), assessing their urinary enzymatic metabolites, 2,3-dinor-6-keto PGF(1α) (PGI-M), 11-dehydro-TXB(2) (TX-M), and 11-α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), respectively. The impact of celecoxib (400 mg b.i.d. for 7 days) on prostanoid biosynthesis and 14 circulating biomarkers of angiogenesis was evaluated in FAP. Intestinal tumorigenesis was associated with enhanced urinary TX-M levels, but unaffected by celecoxib, suggesting the involvement of a COX-1-dependent pathway, presumably from platelets. This was supported by the finding that in cocultures of a human colon adenocarcinoma cell line (HT-29) and platelets enhanced TXA(2) generation was almost completely inhibited by pretreatment of platelets with aspirin, a preferential inhibitor of COX-1. In FAP, celecoxib profoundly suppressed PGE(2) and PGI(2) biosynthesis that was associated with a significant increase in circulating levels of most proangiogenesis proteins but also the antiangiogenic tissue inhibitor of metalloproteinase 2. Urinary PGI-M, but not PGE-M, was negatively correlated with circulating levels of fibroblast growth factor 2 and angiogenin. In conclusion, inhibition of tumor COX-2-dependent PGE(2) by celecoxib may reduce tumor progression. However, the coincident depression of vascular PGI(2), in a context of enhanced TXA(2) biosynthesis, may modulate the attendant angiogenesis, contributing to variability in the chemopreventive efficacy of COX-2 inhibitors such as celecoxib.
organization: G. d'Annunzio University School of MedicineDOI: 10.1124/jpet.111.190785
read more full text source
expertly curated content related to this topic
-
Is Diverting Ileostomy Necessary in Stapled Ileoanal Pouch?Total proctocolectomy with ileal pouch a...
-
Chemo: (Hair) Loss & Mane (Thinning)https://www.youtube.com/watch?v=TaGRE_J5...
-
Outcome Based on Management for Duodenal Adenomas: Sporadic versus Familial DiseaseINTRODUCTION : Management and outcomes f...
-
Long Term Treatment with Sulindac in Familial Adenomatous Polyposis: Is there an Actual Efficiacy in Prevention of ...BACKGROUND AND OBJECTIVES : Ileorectal a...
-
Is Laparoscopic Surgery an Option to Support Prophylactic Colectomy in Adolescent Patients with Familial Adenomatous...BACKGROUND : Prophylactic surgery is sti...
-
Long-Term Outcome of Sporadic and FAP-Associated Desmoid Tumors Treated with High-Dose Selective Estrogen Receptor M...Aim of this study is to evaluate the out...