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Journal of the American Academy of... Oct 2021Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
BACKGROUND
Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
OBJECTIVE
This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed.
METHODS
A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus.
RESULTS
Analysis of the evidence resulted in 18 recommendations.
LIMITATIONS
This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data.
CONCLUSIONS
Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.
Topics: Diclofenac; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Photochemotherapy
PubMed: 33820677
DOI: 10.1016/j.jaad.2021.02.082 -
Theranostics 2022While some non-steroidal anti-inflammatory drugs (NSAIDs) are reported to induce hepatic steatosis, the molecular mechanisms are poorly understood. This study presented...
While some non-steroidal anti-inflammatory drugs (NSAIDs) are reported to induce hepatic steatosis, the molecular mechanisms are poorly understood. This study presented the mechanism by which NSAIDs induce hepatic lipid accumulation. Mouse primary hepatocytes and HepG2 cells were used to examine the underlying mechanism of NSAID-induced hepatic steatosis. Lipid accumulation was measured using Nile-red assay and BODIPY 493/503. The activity of chaperone-mediated autophagy (CMA) was determined by western blotting, qRT-PCR, and confocal imaging. The effect of NSAID on CMA inhibition was evaluated using diclofenac and CMA activator (AR7) administered mice. All tested NSAIDs in this study accumulated neutral lipids in hepatocytes, diclofenac having demonstrated the most potency in that regard. Diclofenac-induced lipid accumulation was confirmed in both mouse primary hepatocytes and the liver of mice. NSAIDs inhibited CMA, as reflected by the decreased expression of lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A) protein, the increased expression of CMA substrate proteins such as PLIN2, and the decreased activity of photoactivatable KFERQ-PAmCherry reporter. Reactivation of CMA by treatment with AR7 or overexpression of LAMP2A inhibited diclofenac-induced lipid accumulation and hepatotoxicity. Upregulation of sorting nexin 10 (SNX10) via the CHOP-dependent endoplasmic reticulum stress response and thus maturation of cathepsin A (CTSA) was shown to be responsible for the lysosomal degradation of LAMP2A by diclofenac. We demonstrated that NSAIDs induced SNX10- and CTSA-dependent degradation of LAMP2A, thereby leading to the suppression of CMA. In turn, impaired CMA failed to degrade PLIN2 and disrupted cellular lipid homeostasis, thus leading to NSAID-induced steatosis and hepatotoxicity.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Autophagy; Chaperone-Mediated Autophagy; Chemical and Drug Induced Liver Injury; Diclofenac; Fatty Liver; Lipids; Lysosomes; Mice; Sorting Nexins
PubMed: 35265214
DOI: 10.7150/thno.70692 -
Journal of Clinical Oncology : Official... May 2024Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS.
METHODS
In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression.
RESULTS
In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4).
CONCLUSION
Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.
Topics: Humans; Capecitabine; Double-Blind Method; Hand-Foot Syndrome; Diclofenac; Female; Male; Middle Aged; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Administration, Topical; Adult; Gastrointestinal Neoplasms; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38412399
DOI: 10.1200/JCO.23.01730 -
Advanced Science (Weinheim,... Feb 2023CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an...
CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an essential role in immune escape, cell proliferation and tumor angiogenesis, making it an attractive target for cancer therapies. However, there are limited clinical benefits associated with the mainstream enzymatic inhibitors of CD73, suggesting that the mechanism underlying the role of CD73 in tumor progression is more complex than anticipated, and further investigation is necessary. In this study, CD73 is found to overexpress in the cytoplasm of pancreatic ductal adenocarcinoma (PDAC) cells and promotes metastasis in a nucleotidase-independent manner, which cannot be restrained by the CD73 monoclonal antibodies or small-molecule enzymatic inhibitors. Furthermore, CD73 promotes the metastasis of PDAC by binding to the E3 ligase TRIM21, competing with the Snail for its binding site. Additionally, a CD73 transcriptional inhibitor, diclofenac, a non-steroidal anti-inflammatory drug, is more effective than the CD73 blocking antibody for the treatment of PDAC metastasis. Diclofenac also enhances the therapeutic efficacy of gemcitabine in the spontaneous KPC (LSL-Kras , LSL-Trp53 , and Pdx-1-Cre) pancreatic cancer model. Therefore, diclofenac may be an effective anti-CD73 therapy, when used alone or in combination with gemcitabine-based chemotherapy regimen, for metastatic PDAC.
Topics: Humans; Carcinoma, Pancreatic Ductal; Diclofenac; Gemcitabine; Pancreatic Neoplasms; Nucleotidases
PubMed: 36563135
DOI: 10.1002/advs.202206335 -
ACS Nano Dec 2023Meniscus injuries are associated with the degeneration of cartilage and development of osteoarthritis (OA). It is challenging to protect articular cartilage and improve...
Meniscus injuries are associated with the degeneration of cartilage and development of osteoarthritis (OA). It is challenging to protect articular cartilage and improve exercise when a meniscus injury occurs. Herein, inspired by the components and functions of the meniscus, we developed a self-lubricating and friction-responsive hydrogel that contains nanoliposomes loaded with diclofenac sodium (DS) and Kartogenin (KGN) for anti-inflammation and cartilage regeneration. When the hydrogel was injected into the meniscus injury site, the drug-loaded nanoliposomes were released from the hydrogel in a friction-responsive manner and reassembled to form hydration layers that lubricate joints during movement. Meanwhile, DS and KNG were constantly released from the nanoliposomes to mitigate inflammation and promote cartilage regeneration. Additionally, this hydrogel exhibited favorable injectability, mechanical properties, fatigue resistance, and prolonged degradation. experiments demonstrated that injection of the hydrogel effectively improved exercise performance and protected the articular cartilage of rats, suggesting it as a potential therapeutic approach for meniscal injuries.
Topics: Rats; Animals; Cartilage, Articular; Hydrogels; Friction; Meniscus; Injections; Diclofenac
PubMed: 37975685
DOI: 10.1021/acsnano.3c10139 -
Andrologia Jun 2021Diclofenac is an effective nonsteroidal anti-inflammatory drug and one of the most prescribed medicines worldwide. So far, there are many published articles that... (Review)
Review
Diclofenac is an effective nonsteroidal anti-inflammatory drug and one of the most prescribed medicines worldwide. So far, there are many published articles that directly link between diclofenac and semen quality; however, hitherto, there is no collective review or comprehensive discussion that reveal such imperative link. Therefore, this work reviews and judges the association between diclofenac administration and semen quality, henceforth male infertility. As a tool to accomplish this scientific input, Scopus, Embase and PubMed databases have been searched for all original articles using the keywords "diclofenac" versus "semen" and "sperm" since August 1987 through November 2020. In summary, diclofenac appears to induce negative effects on both qualitative and quantitative measures of sperm; however, this conclusion requires confirmation by human studies. The detected negative effects of diclofenac on semen quality measures may be owed to reduced levels of gonadal hormones, decreased antioxidant defence mechanism, increased oxidative stress, altered concentrations of nitric oxide that are required to maintain normal sperm physiology and reduced synthesis of prostaglandins.
Topics: Diclofenac; Humans; Infertility, Male; Male; Semen; Semen Analysis; Spermatozoa
PubMed: 33650710
DOI: 10.1111/and.14021 -
The Science of the Total Environment Nov 2021Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in livestock farming, with lethal effects on vultures when reaching high concentrations in the... (Review)
Review
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in livestock farming, with lethal effects on vultures when reaching high concentrations in the carcasses they feed on. There are evidences showing that it caused the decline of >95% of vultures of the Gyps genus in Southern Asia until its ban in 2006. In March 2013 two veterinary drugs containing diclofenac were authorized in Spain. The scientific and conservationist communities alerted on the foreseeable risks to European vulture populations based on previous experiences. Several risk assessments modelled the expected impact on vultures, and media campaigns were launched to ban the veterinary use of diclofenac. Here, we evaluate the situation of Spanish vultures after seven years (2013-2019) since the marketing authorisation of the veterinary use of diclofenac was granted. The present assessment takes into consideration the awareness measures adopted to avoid an inappropriate use of the drug, the results of the monitoring programs performed both for vultures and livestock in the wild and from toxicological tests, as well as the review of the published models on the expected mortality of vultures. The measures adopted seem to have been adequate and have avoided impacts at vulture population level despite the finding of one cinereous vulture lethally intoxicated by diclofenac in 2020. In view of the results, we discuss the different situations from the veterinary use of this drug between Southern Asia and Spain. Finally, surveillance priorities and future prospects are proposed to prevent risks from possible changes in the current circumstances, regarding the use of diclofenac and other NSAIDs potentially harmful like flunixin.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Falconiformes; Spain; Veterinary Drugs
PubMed: 34271379
DOI: 10.1016/j.scitotenv.2021.148851 -
General Dentistry 2021
Review
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dentists; Diclofenac; Humans
PubMed: 33908871
DOI: No ID Found -
Journal of Chromatographic Science Dec 2023A reversed-phase high-performance liquid chromatography method was developed and validated for the simultaneous determination of pridinol, diclofenac and...
A reversed-phase high-performance liquid chromatography method was developed and validated for the simultaneous determination of pridinol, diclofenac and diclofenac-related compounds in tablet formulations. The proposed method is also suitable for content uniformity determination, for dissolution test and for stability studies. Separation was achieved on a base-deactivated silica C8 column, using 50 mM phosphate buffer (pH 2.5) and methanol (40:60 v/v) as mobile phase, at a flow rate of 1.0 mL/min and column temperature of 40°C. Ultraviolet detection was made at 225 nm. The method was validated for specificity, accuracy, precision (intraday and interday levels) and linearity for each analyte. For diclofenac impurity A, sensitivity was also studied. The method showed specificity and linearity (R2: 0.999 for the three analytes) over the assessed concentration range (diclofenac: 2.5-75.0 μg/mL, pridinol: 2.0-60.0 μg/mL and impurity A: 1.25-5.0 μg/mL) and demonstrated good precision as reflected by the low coefficient of variation in all cases. Recovery rates obtained were 99.81, 100.58 and 100.96% for diclofenac, pridinol and impurity A respectively, and for all three analytes, the variances of the concentrations tested were equivalent. The detection and quantitation limits for impurity A were 0.078 and 0.261 μg/mL, respectively.
Topics: Diclofenac; Chromatography, High Pressure Liquid; Piperidines; Tablets
PubMed: 36912069
DOI: 10.1093/chromsci/bmad017 -
Molecules (Basel, Switzerland) Oct 2019The presence of pharmaceutical compounds in the environment is a reality that calls for more efficient water treatment technologies. Photocatalysis is a powerful... (Review)
Review
The presence of pharmaceutical compounds in the environment is a reality that calls for more efficient water treatment technologies. Photocatalysis is a powerful technology available but the high energy costs associated with the use of UV irradiation hinder its large scale implementation. More sustainable and cheaper photocatalytic processes can be achieved by improving the sunlight harvesting and the synthesis of semiconductor/carbon composites has proved to be a promising strategy. Carbamazepine, diclofenac, and sulfamethoxazole were selected as target pharmaceuticals due to their recalcitrant behavior during conventional wastewater treatment and persistence in the environment, as properly reviewed. The literature data on the photocatalytic removal of carbamazepine, diclofenac, and sulfamethoxazole by semiconductor/carbon materials was critically revised to highlight the role of the carbon in the enhanced semiconductor performance under solar irradiation. Generally it was demonstrated that carbon materials induce red-shift absorption and they contribute to more effective charge separation, thus improving the composite photoactivity. Carbon was added as a dopant (C-doping) or as support or doping materials (i.e nanoporous carbons, carbon nanotubes (CNTs), graphene, and derived materials, carbon quantum dots (CQDs), and biochars) and in the large majority of the cases, TiO was the semiconductor tested. The specific role of carbon materials is dependent on their properties but even the more amorphous forms, like nanoporous carbons or biochars, allow to prepare composites with improved properties compared to the bare semiconductor. The self-photocatalytic activity of the carbon materials was also reported and should be further explored. The removal and mineralization rates, as well as degradation pathways and toxicity of the treated solutions were also critically analyzed.
Topics: Carbamazepine; Catalysis; Diclofenac; Graphite; Photochemical Processes; Semiconductors; Sulfamethoxazole; Sunlight; Water Pollutants, Chemical
PubMed: 31618947
DOI: 10.3390/molecules24203702