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1.
Sci Rep ; 11(1): 23658, 2021 Dec 08.
Article in English | MEDLINE | ID: mdl-34880320

ABSTRACT

The design, preparation and characterization of a novel composite based on functionalization of halloysite nanoclay with Schiff base followed by immobilization of copper iodide as nanoparticles is revealed. This novel nano composite was fully characterized by utilization of FTIR, SEM/EDX, TGA, XRD and BET techniques. This Cu(I) NPs immobilized onto halloysite was successfully examined as a heterogeneous, thus easily recoverable and reusable catalyst in one of classist organic name reaction so-called "Click Reaction". That comprised a three component reaction of phenylacetylene, α-haloketone or alkyl halide and sodium azide in aqueous media to furnish 1,2,3-triazoles in short reaction time and high yields. Remarkably, the examination of the reusability of the catalyst confirmed that the catalyst could be reused at least six reaction runs without appreciable loss of its catalytic activity.

2.
Cancer Prev Res (Phila) ; 2(4): 310-21, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19336730

ABSTRACT

The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of the cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk for colorectal cancer. The trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. The primary study safety and efficacy analyses involved 3 years of treatment. The results showed significant antitumor effect but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared with placebo. A total of 933 patients participated in an extension of the Adenoma Prevention with Celecoxib Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years for those with a year 5 colonoscopy. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (P < 0.0001) for those receiving low-dose celecoxib, and 60.1% (P < 0.0001) for those receiving high-dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (P < 0.0001) of those taking low dose celecoxib and 15.8% (P < 0.0001) of those taking high-dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95% confidence interval, 1.0, 2.5) for those using 200 mg twice daily celecoxib and 1.9 (95% confidence interval, 1.2, 3.1) for those using 400 mg twice daily celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (P = 0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety data indicating an elevated risk for cardiovascular and thrombotic adverse events, particularly for patients with preexisting atherosclerotic heart disease.


Subject(s)
Adenoma/prevention & control , Cardiovascular Diseases/chemically induced , Colorectal Neoplasms/prevention & control , Cyclooxygenase 2 Inhibitors/adverse effects , Pyrazoles/adverse effects , Sulfonamides/adverse effects , Adult , Aged , Aged, 80 and over , Celecoxib , Colonoscopy , Cyclooxygenase 2 Inhibitors/administration & dosage , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage
3.
N Engl J Med ; 355(9): 873-84, 2006 Aug 31.
Article in English | MEDLINE | ID: mdl-16943400

ABSTRACT

BACKGROUND: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. METHODS: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test. RESULTS: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9). CONCLUSIONS: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).


Subject(s)
Adenoma/prevention & control , Colorectal Neoplasms/prevention & control , Cyclooxygenase 2 Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adenoma/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/mortality , Celecoxib , Colorectal Neoplasms/drug therapy , Cyclooxygenase 2 Inhibitors/administration & dosage , Cyclooxygenase 2 Inhibitors/adverse effects , Drug Therapy, Combination , Female , Gastrointestinal Diseases/chemically induced , Humans , Kidney Diseases/chemically induced , Male , Middle Aged , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Secondary Prevention , Sulfonamides/administration & dosage , Sulfonamides/adverse effects
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