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The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.

ABSTRACT: Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclo-oxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action of PXM on the pathogenesis of nonmelanoma skin cancer, analyzing and evaluating binding modes and energies between COX-1 or COX-2 and PXM by protein-ligand molecular docking. Our clinical experience about the local use of PXM on actinic keratoses and field cancerization is also reported, confirming its efficacy as target therapy.

SUBMITTER: Campione E

PROVIDER: S-EPMC4630202 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.

Campione Elena E Paternò Evelin Jasmine EJ Candi Eleonora E Falconi Mattia M Costanza Gaetana G Diluvio Laura L Terrinoni Alessandro A Bianchi Luca L Orlandi Augusto A

Drug design, development and therapy 20151029

Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclo-oxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppress ...[more]

PMID: 26604686

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Project description:IMPORTANCE:Immune dysfunction underlies the pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunosuppressive therapy is the standard of care for these diseases. Both immune dysfunction and therapy-related immunosuppression can inhibit cancer-related immune surveillance in this population. Drug-induced immunosuppression is a risk factor for nonmelanoma skin cancer (NMSC), particularly squamous cell tumors. For patients with a history of NMSC, data are limited on the effect of these drugs on the risk of additional NMSCs. OBJECTIVE:To determine the relative hazard of a second NMSC in patients with RA or IBD who use methotrexate, anti-tumor necrosis factor (anti-TNF) therapy, or thiopurines after an initial NMSC. DESIGN, SETTING, AND PARTICIPANTS:In this retrospective cohort study, we studied 9460 individuals with RA or IBD enrolled in Medicare from January 1, 2006, through December 31, 2012. EXPOSURES:Exposure to methotrexate, thiopurines, anti-TNFs, sulfasalazine, hydroxychloroquine, abatacept, or rituximab after the incident NMSC surgery. MAIN OUTCOMES AND MEASURES:A second NMSC occurring 1 year or more after the incident NMSC using Cox proportional hazards regression models. RESULTS:Among 9460 individuals (6841 with RA and 2788 with IBD), the incidence rate of a second NMSC per 1000 person-years was 58.2 (95% CI, 54.5-62.1) and 58.9 (95% CI, 53.2-65.2) in patients with RA and IBD, respectively. Among patients with RA, methotrexate used in conjunction with other medications was associated with an increased risk of a second NMSC (hazard ratio [HR], 1.60; 95% CI, 1.08-2.37). Adjusted for other medications, the risk of NMSC increased with 1 year or more of methotrexate use (HR, 1.24; 95% CI, 1.04-1.48). Compared with methotrexate alone, the addition of anti-TNF drugs was significantly associated with risk of NMSC (HR, 1.49; 95% CI, 1.03-2.16). Abatacept and rituximab were not associated with increased NMSC risk. The nonsignificant HRs for 1 year or more of thiopurine and anti-TNF use for IBD were 1.49 (95% CI, 0.98-2.27) and 1.36 (95% CI, 0.76-2.44), respectively. CONCLUSIONS AND RELEVANCE:Methotrexate use is associated with an increased risk of a second NMSC. Anti-TNF use may increase the risk of a second NMSC when used with methotrexate for RA. Further long-term studies are required before one can conclude that thiopurine and/or anti-TNF do not increase the risk of a second NMSC in patients with IBD.

Project description:BackgroundNonmelanoma skin cancer (NMSC) affects many Canadians. Although morbidity and mortality are rare, the burden to patients and the health-care system is significant. This study aims to evaluate current plastic surgery wait times and care pathways for patients with NMSC in Southwestern Ontario.MethodsA retrospective chart review of 225 patients treated in Ontario from 2015 to 2018 was conducted. Inclusion criteria included patients with an NMSC managed with surgical excision. Referral information was compared. Primary outcomes were wait times: from referral to consultation, referral to excision, and consultation to excision. Data were analyzed using Student t test with equal variance.ResultsOne-hundred forty-three patients were included from the academic cohort and 82 from the community cohort. Referrals to academic and community surgeons included lesion location (90% and 97.6%, respectively), but less frequently included size (18% and 29.2%, respectively). Most referrals to academic surgeons included biopsy results (78.6%), as opposed to community referrals (25.6%). Patients in the academic cohort waited 15.3 ± 12.7 weeks from referral to consultation, and 15.7 ± 13 weeks from referral to excision. Patients from the community cohort waited significantly shorter periods of 4.9 ± 3.1 (P < .001) and 11.7 ± 9.9 weeks (P = .016), respectively. However, patients of the academic cohort waited 2.4 ± 7.1 weeks from consultation to excision, while patients in the community cohort waited 6.7 ± 9.6 weeks (P < .001). Rates of negative peripheral margins on pathology were similar between groups, at 89.5% of the academic cohort and 88.9% of the community cohort. Deep margins were positive 5.7% of the time at the academic sites and 6.2% of the time in the community.ConclusionsPatients referred to academic centres waited significantly longer periods of time in several parameters compared to those referred to a community surgeon. However, academic surgeons often had expedited consultation-to-excision time frame. This study provides important data for future quality improvement initiatives in NMSC care.

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The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.

Publications

The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.

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