Platelet activation in patients with colorectal cancer.
Aspirin may reduce the risk of colorectal neoplasia at doses similar to those recommended for the prevention of cardiovascular disease. Thus, we aimed to address whether enhanced platelet activation, as assessed by the measurement of the urinary excretion of 11-dehydro-TXB(2) (a major enzymatic metabolite of TXB(2)), occurs in patients with colorectal cancer. In 10 patients with colorectal cancer, the urinary excretion of 11-dehydro-TXB(2) was significantly higher than in 10 controls, matched for sex, age and cardiovascular risk factors [1001(205-5571) versus 409(113-984) pg/mg creatinine, respectively, median (range), P<0.05]. The administration of aspirin 50 mg daily for 5 consecutive days to colorectal cancer patients caused a cumulative inhibition of platelet cyclooxygenase (COX)-1 activity either ex vivo, as assessed by the measurement of serum TXB(2) levels, or in vivo, as assessed by urinary 11-dehydro-TXB(2) excretion. In conclusion, enhanced platelet activation occurs in colorectal cancer patients. Permanent inactivation of platelet COX-1 by low-dose aspirin might restore anti-tumor reactivity.
Sciulli
M G
MG
Department of Medicine and Center of Excellence on Aging, G. d'Annunzio University, School of Medicine, 66013 Chieti, Italy.
Filabozzi
P
P
Tacconelli
S
S
Padovano
R
R
Ricciotti
E
E
Capone
M L
ML
Grana
M
M
Carnevale
V
V
Patrignani
P
P
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D015415:Biomarkers / Q000652:urine; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine*
D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin