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[PMID]:29357800
[Au] Autor:Siverio-Mota D; Andujar I; Marrero-Ponce Y; Giner RM; Diaz-Mendoza C; Paba GM; Vicet-Muro L; Cordero-Maldonado ML; de Witte PAM; Crawford AD; Veitia MS; Perez-Jimenez F; Aran VJ
[Ad] Endereço:Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
[Ti] Título:Anti-Inflammatory Activity and Cheminformatics Analysis of New Poten t 2-Substituted 1-Methyl-5-Nitroindazolinones.
[So] Source:Curr Top Med Chem;17(30):3236-3248, 2018 Feb 09.
[Is] ISSN:1873-4294
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:After the identification of the anti-inflammatory properties of VA5-13l (2-benzyl-1- methyl-5-nitroindazolinone) in previous investigations, some of its analogous compounds were designed, synthesized and evaluated in two anti-inflammatory methods: LPS-enhanced leukocyte migration assay in zebrafish; and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. The products evaluated (3, 6, 8, 9 and 10) showed the lower values of relative leukocyte migration at 30 µM (0.14, 0.07, 0.10, 0.13 and 0.07, respectively), while in ear edema and myeloperoxidase activity methods, all the compounds reduced inflammation, only 4 and 16 yielded unsatisfactory results. The relationship linking structure and activity (SAR analysis) was determinate by using SARANEA software. The importance of the 5-Nitro group of the indazole ring for the activity was evident, and showed modest reduction when benzyl (Bn) is changed by alkyl group. A substituted Bn moiety at N2 (R) is the best substituent (5-10); nevertheless, if methylene group of Bn is deleted, the activity is affected. Also, introduction of halogen atoms mainly at positions 3 or 4 of the benzyl moiety (6 and 10) leads in general to strong activities. In fact, compounds 7 and 8 (R = 4-FBn or 4-ClBn, respectively) exhibit satisfactory results in in vivo tests and appear promising. The production of IL-6 at all doses assayed was significantly reduced, except with 16. Nonetheless, the production of TNF-α was significantly inhibited only by this chemical (16) at concentration of 50 µM. On the other hand, compound 2 was the one that mostly inhibited the expression of COX-2 and iNOS. From these results, it can be concluded that the inhibition in the release of cytokines can be one of the mechanisms of action responsible for the anti-inflammatory effect for 2-benzyl derivates while other 2-alkyl derivatives can inhibit production of NO. Therefore, nitroindazolinone chemical prototype could be an interesting structural group with anti-inflammatory purposes in the therapeutic.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Inibidores de Ciclo-Oxigenase 2/farmacologia
Indazóis/farmacologia
Informática
Nitrocompostos/farmacologia
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/química
Ciclo-Oxigenase 2/metabolismo
Inibidores de Ciclo-Oxigenase 2/química
Relação Dose-Resposta a Droga
Seres Humanos
Indazóis/química
Lipopolissacarídeos/antagonistas & inibidores
Lipopolissacarídeos/farmacologia
Estrutura Molecular
Óxido Nítrico/antagonistas & inibidores
Óxido Nítrico/biossíntese
Óxido Nítrico Sintase Tipo II/antagonistas & inibidores
Óxido Nítrico Sintase Tipo II/metabolismo
Nitrocompostos/química
Relação Estrutura-Atividade
Fator de Necrose Tumoral alfa/antagonistas & inibidores
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cyclooxygenase 2 Inhibitors); 0 (Indazoles); 0 (Lipopolysaccharides); 0 (Nitro Compounds); 0 (Tumor Necrosis Factor-alpha); 31C4KY9ESH (Nitric Oxide); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.99.1 (Cyclooxygenase 2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE
[do] DOI:10.2174/1568026618666180119125255


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[PMID]:29199735
[Au] Autor:Elsayed MSA; Chang S; Cushman M
[Ad] Endereço:Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, USA. cushman@purdue.edu.
[Ti] Título:Ligand-free, palladacycle-facilitated Suzuki coupling of hindered 2-arylbenzothiazole derivatives yields potent and selective COX-2 inhibitors.
[So] Source:Org Biomol Chem;16(1):108-118, 2017 Dec 19.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A similarity search and molecular modeling study suggested the 2'-aryl-2-arylbenzothiazole framework as a novel scaffold for the design of COX-2-selective inhibitors. Conventional Suzuki coupling conditions did not furnish the designed compounds in good yield from 2'-bromo-2-arylbenzothiazole as the starting material. A novel ligand-free Suzuki-Miyaura coupling methodology was developed for sterically hindered 2'-bromo-2-arylbenzothiazoles. The reaction depends on the coordination properties of the benzothiazole ring nitrogen, which is involved in the formation of a palladacyclic intermediate that was synthesized independently and converted to the final product. The new method provides good to excellent yields (up to 99%) with favorable functional group tolerability. Six compounds had potencies in the submicromolar range against COX-2 and higher selectivity for COX-2 vs. COX-1 compared to the currently used drug celecoxib. Molecular modeling was used to investigate the possible binding mode with COX-2.
[Mh] Termos MeSH primário: Benzotiazóis/farmacologia
Inibidores de Ciclo-Oxigenase 2/farmacologia
Ciclo-Oxigenase 2/metabolismo
[Mh] Termos MeSH secundário: Benzotiazóis/síntese química
Benzotiazóis/química
Inibidores de Ciclo-Oxigenase 2/síntese química
Inibidores de Ciclo-Oxigenase 2/química
Relação Dose-Resposta a Droga
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzothiazoles); 0 (Cyclooxygenase 2 Inhibitors); EC 1.14.99.1 (Cyclooxygenase 2); G5BW2593EP (benzothiazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1039/c7ob02386c


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[PMID]:29385156
[Au] Autor:Lu CH; Chung CH; Lee CH; Hsieh CH; Hung YJ; Lin FH; Tsao CH; Hsieh PS; Chien WC
[Ad] Endereço:Department of Internal Medicine, Division of Endocrinology and Metabolism, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.
[Ti] Título:Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.
[So] Source:PLoS One;13(1):e0191242, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone. METHODS: In total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up. RESULTS: At the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601-0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without. CONCLUSIONS: Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination therapy much more decrease pro-inflammatory factors associated than those without metformin therapy.
[Mh] Termos MeSH primário: Artroplastia de Substituição
Inibidores de Ciclo-Oxigenase 2/administração & dosagem
Diabetes Mellitus Tipo 2/complicações
Diabetes Mellitus Tipo 2/tratamento farmacológico
Hipoglicemiantes/administração & dosagem
Metformina/administração & dosagem
Osteoartrite/complicações
Osteoartrite/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Artroplastia de Substituição/estatística & dados numéricos
Estudos de Coortes
Quimioterapia Combinada
Feminino
Seres Humanos
Masculino
Meia-Idade
Osteoartrite/cirurgia
Modelos de Riscos Proporcionais
Estudos Retrospectivos
Taiwan
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cyclooxygenase 2 Inhibitors); 0 (Hypoglycemic Agents); 9100L32L2N (Metformin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191242


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[PMID]:29390421
[Au] Autor:Guo Q; Liu X; Lu L; Yuan H; Wang Y; Chen Z; Ji R; Zhou Y
[Ad] Endereço:Department of Gastroenterology.
[Ti] Título:Comprehensive evaluation of clinical efficacy and safety of celecoxib combined with chemotherapy in management of gastric cancer.
[So] Source:Medicine (Baltimore);96(51):e8857, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: To evaluate the clinical efficacy and safety of celecoxib combined with chemotherapy in the treatment of gastric cancer. METHODS: In total, 240 gastric cancer patients undergoing radical gastrectomy followed by adjuvant chemotherapy were randomly assigned into 2 groups. In the experimental group (n = 120), patients were administered with celecoxib-based chemotherapy, and chemotherapy alone was performed in the control group. Disease-free survival (DFS) and progression-free survival (PFS) were considered as the primary efficacy parameters, and objective response rate (ORR), overall survival (OS), quality of life (QOL), and safety as the secondary efficacy parameters. RESULTS: The 3-year OS did not significantly differ between the experimental (72%) and control groups (68%, P = .67). The 3-year DFS in the experimental group was 64%, which did not significantly differ from 51% in the control group (P = .41). In patients with positive cyclooxygenase-2 (COX-2) from the experimental group, the 3-year OS was 78%, significantly higher compared with 66% in the control group (P = .02), and the 3-year DFS was 70%, considerably >50% in the control group (P = .01). No statistical significance was identified in the incidence of nausea, neutropenia, anorexia, peripheral neurotoxicity, diarrhea, vomiting, asthenia, and thrombocytopenia, etc. The EORTC quality of life questionnaire (QLQ)-C30 questionnaire revealed that the global QOL in the experimental group was significantly higher than that in the control group (P < .05). No statistical significance was noted in the scores of functioning scale between 2 groups, whereas the scores of the symptom scale, especially pain and fatigue in the experimental group were remarkably higher than that in the control group (P < .05). The global score of EORTC QLQ-STO22 in the experimental group was considerably higher compared with that in the control group (P < .05). No statistical significance was identified in term of the domains of restrictions on feeding, dysphagia, anxiety, reflux, sense of taste, dry mouth, hair loss, and body shape between groups (all P > .05). CONCLUSION: Celecoxib combined with chemotherapy yields clinical benefits for gastric cancer patients with positive COX-2, which not only enhances the OS, DFS, PFS, QOL, and short-term clinical efficacy, but also does not increase the risk of adverse events.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Celecoxib/uso terapêutico
Inibidores de Ciclo-Oxigenase 2/uso terapêutico
Qualidade de Vida
Neoplasias Gástricas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adenocarcinoma/mortalidade
Adenocarcinoma/patologia
Adenocarcinoma/psicologia
Adolescente
Adulto
Idoso
Protocolos de Quimioterapia Combinada Antineoplásica
Celecoxib/administração & dosagem
Quimioterapia Adjuvante
China
Inibidores de Ciclo-Oxigenase 2/administração & dosagem
Intervalo Livre de Doença
Feminino
Gastrectomia
Seres Humanos
Masculino
Meia-Idade
Neoplasias Gástricas/mortalidade
Neoplasias Gástricas/patologia
Neoplasias Gástricas/psicologia
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Cyclooxygenase 2 Inhibitors); JCX84Q7J1L (Celecoxib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008857


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[PMID]:29382005
[Au] Autor:Zhang H; Yang B
[Ad] Endereço:Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
[Ti] Título:Successful treatment of pachydermoperiostosis patients with etoricoxib, aescin, and arthroscopic synovectomy: Two case reports.
[So] Source:Medicine (Baltimore);96(47):e8865, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Pachydermoperiostosis (PDP) is a rare hereditary disorder that affects the skin and bones. PDP is characterized by periostosis, digital clubbing, and pachydermia. Previous studies demonstrated that increased prostaglandin E2 (PGE2) levels resulting from defective protein degradation pathways play a crucial role in PDP pathogenesis, and males were more commonly and severely affected than females. Moreover, nearly all PDP patients suffer from refractory arthralgia. Although several different treatment modalities are used for PDP, therapy for this disease remains challenging. PATIENTS CONCERNS: Two cases of PDP showing symptoms consistent with polyarthritis and arthralgia that mainly affected the knees and ankles. DIAGNOSES: The diagnostic criteria for PDP include digital clubbing, periostosis, and pachydermia. The 2 patients were diagnosed as PDP based on the finger clubbing, facial cutis furrowing, knee and ankle arthritis, and radiographic evidence of periosteal proliferation. INTERVENTIONS: Patient 1 had massive joint effusion that was treated by oral administration of etoricoxib and aescin combined with arthroscopic synovectomy, whereas Patient 2 had mild joint swelling and accepted only oral medication. OUTCOMES: Clinical symptoms of the 2 patients greatly improved after the treatment. During the 1-year follow-up, the patient experienced no adverse effects or recurrence. LESSONS: The therapeutic results showed that oral etoricoxib could reduce inflammation and retard progression of pachydermia, or even relieve facial skin furrowing, but had limited efficacy for arthralgia. However, oral aescin had satisfactory efficacy for arthralgia. Thus, etoricoxib combined with aescin is a safe and effective treatment for PDP. Meanwhile, arthroscopic synovectomy can be used to treat joint effusion, but had no therapeutic effect on arthralgia. Therefore, postoperative oral medications would be needed as subsequent therapy for joint problems. In conclusion, this study proposes an effective and safe treatment plan to address symptoms experienced by PDP patients.
[Mh] Termos MeSH primário: Fármacos Cardiovasculares/administração & dosagem
Inibidores de Ciclo-Oxigenase 2/administração & dosagem
Escina/administração & dosagem
Osteoartropatia Hipertrófica Primária/terapia
Piridinas/administração & dosagem
Sulfonas/administração & dosagem
Sinovectomia/métodos
[Mh] Termos MeSH secundário: Artroscopia
Terapia Combinada
Seres Humanos
Masculino
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiovascular Agents); 0 (Cyclooxygenase 2 Inhibitors); 0 (Pyridines); 0 (Sulfones); 6805-41-0 (Escin); WRX4NFY03R (etoricoxib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008865


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[PMID]:29374758
[Au] Autor:Friedrich M; Reichert K; Woeste A; Polack S; Fischer D; Hoellen F; Rody A; Köster F; Thill M
[Ad] Endereço:Department of Gynecology and Obstetrics, Helios Hospital Krefeld, Krefeld, Germany michael.friedrich@helios-kliniken.de.
[Ti] Título:Effects of Combined Treatment with Vitamin D and COX2 Inhibitors on Breast Cancer Cell Lines.
[So] Source:Anticancer Res;38(2):1201-1207, 2018 02.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Vitamin D is known for its anticancer potential. Prostaglandin E (PGE ) is a proliferative and inflammation-activating agent. The production of PGE is dependent on the activity of cyclooxygenase-2 (COX2). A link between vitamin D and PGE metabolism was shown recently. MATERIALS AND METHODS: In MDA-MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as well as on the protein and mRNA expression of COX2 using western blot and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX2 inhibitor celecoxib and even more strongly by their combination. Moreover, calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2 mRNA expression in both cell lines. CONCLUSION: The combination of calcitriol and celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer cell lines.
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
Calcitriol/farmacologia
Celecoxib/farmacologia
Inibidores de Ciclo-Oxigenase 2/farmacologia
Vitaminas/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Neoplasias da Mama/tratamento farmacológico
Proliferação Celular/efeitos dos fármacos
Quimioterapia Combinada
Feminino
Seres Humanos
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclooxygenase 2 Inhibitors); 0 (Vitamins); FXC9231JVH (Calcitriol); JCX84Q7J1L (Celecoxib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180129
[St] Status:MEDLINE


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[PMID]:29201297
[Au] Autor:Lee M; Yoo J; Kim JG; Kyung HS; Bin SI; Kang SB; Choi CH; Moon YW; Kim YM; Han SB; In Y; Choi CH; Kim J; Lee BK; Cho S
[Ad] Endereço:Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea.
[Ti] Título:A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis.
[So] Source:Clin Orthop Surg;9(4):439-457, 2017 Dec.
[Is] ISSN:2005-4408
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:Background: The aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA). Methods: This study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations. Results: After 6 weeks, the polmacoxib-placebo treatment difference was -2.5 (95% confidence interval [CI], -4.4 to -0.6; = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, -0.9 to 2.2; = 0.425). According to Physician's Global Assessments, more subjects were "much improved" at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo. Conclusions: Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.
[Mh] Termos MeSH primário: Celecoxib/uso terapêutico
Inibidores de Ciclo-Oxigenase 2/uso terapêutico
Furanos/uso terapêutico
Dor Musculoesquelética/tratamento farmacológico
Osteoartrite do Quadril/tratamento farmacológico
Osteoartrite do Joelho/tratamento farmacológico
Sulfonamidas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Celecoxib/efeitos adversos
Inibidores de Ciclo-Oxigenase 2/efeitos adversos
Método Duplo-Cego
Feminino
Furanos/efeitos adversos
Gastroenteropatias/induzido quimicamente
Seres Humanos
Masculino
Meia-Idade
Dor Musculoesquelética/etiologia
Osteoartrite do Quadril/complicações
Osteoartrite do Quadril/fisiopatologia
Osteoartrite do Joelho/complicações
Osteoartrite do Joelho/fisiopatologia
Amplitude de Movimento Articular
Sulfonamidas/efeitos adversos
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; EQUIVALENCE TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (CG100649); 0 (Cyclooxygenase 2 Inhibitors); 0 (Furans); 0 (Sulfonamides); JCX84Q7J1L (Celecoxib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.4055/cios.2017.9.4.439


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[PMID]:29320568
[Au] Autor:Feng X; Tian M; Zhang W; Mei H
[Ad] Endereço:Department of Nephrology and Rheumatology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, China.
[Ti] Título:Gastrointestinal safety of etoricoxib in osteoarthritis and rheumatoid arthritis: A meta-analysis.
[So] Source:PLoS One;13(1):e0190798, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To ascertain if etoricoxib increases the risk of gastrointestinal adverse events (GAEs) compared with placebo, diclofenac, and naproxen in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA). METHODS: Studies were searched in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials from inception to August 2017. Randomized Clinical Trials (RCTs) that compared etoricoxib with placebo and other active drug for patients with OA or RA and reported data on gastrointestinal safety (which is of interest to patients and clinicians) were included. The follow-up time window for GAEs was defined as within 28 days subsequent to the last dose of study medication. A meta-analysis was conducted using a fixed-effect model. Risk ratios (RRs) and 95% confidence intervals (CIs) were measured. RESULTS: We found nine randomized clinical trials (RCTs) that included information on gastrointestinal safety during follow-up time. Among them, five RCTs compared etoricoxib with placebo, four RCTs compared etoricoxib with diclofenac, and three RCTs compared etoricoxib with naproxen. Etoricoxib did not increase the risk of GAEs compared with placebo. Compared with diclofenac and naproxen, etoricoxib reduced the GAE risk (RR, 0.67; 95% CI, 0.59-0.76; p < 0.00001; 0.59; 0.48-0.72; < 0.00001) during follow-up time. CONCLUSIONS: In patients with OA or RA, etoricoxib did not increase the GAE risk compared with placebo, but reduced the GAE risk effectively compared with diclofenac and naproxen during follow-up time.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/efeitos adversos
Artrite Reumatoide/tratamento farmacológico
Inibidores de Ciclo-Oxigenase 2/efeitos adversos
Osteoartrite/tratamento farmacológico
Piridinas/efeitos adversos
Sulfonas/efeitos adversos
[Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/uso terapêutico
Inibidores de Ciclo-Oxigenase 2/uso terapêutico
Diclofenaco/efeitos adversos
Diclofenaco/uso terapêutico
Seres Humanos
Naproxeno/efeitos adversos
Naproxeno/uso terapêutico
Piridinas/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Sulfonas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cyclooxygenase 2 Inhibitors); 0 (Pyridines); 0 (Sulfones); 144O8QL0L1 (Diclofenac); 57Y76R9ATQ (Naproxen); WRX4NFY03R (etoricoxib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190798


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[PMID]:29202630
[Au] Autor:Cronin-Fenton D; Lash TL; Ahern TP; Damkier P; Christiansen P; Ejlertsen B; Sørensen HT
[Ad] Endereço:a Department of Clinical Epidemiology , Aarhus University , Aarhus , Denmark.
[Ti] Título:Concurrent new drug prescriptions and prognosis of early breast cancer: studies using the Danish Breast Cancer Group clinical database.
[So] Source:Acta Oncol;57(1):120-128, 2018 Jan.
[Is] ISSN:1651-226X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter the viability of breast cancer cells in pre-clinical studies. Routine use of these drugs, therefore, may impact breast cancer prognosis, and could have important implications for public health. METHODS: The Danish Breast Cancer Group (DBCG) clinical database provides high-quality prospectively collected data on breast cancer diagnosis, treatment, and routine follow-up for breast cancer recurrence. Individual-level linkage of DBCG data to other population-based and medical registries in Denmark, including the Danish National Prescription Registry, has facilitated large population-based pharmacoepidemiology studies. A unique advantage of using DBCG data for such studies is the ability to investigate the association of drugs with breast cancer recurrence rather than breast cancer mortality - which may be misclassified - or all-cause mortality. Here we summarize findings from pharmacoepidemiological studies, based on DBCG data, on the association between routinely used prescription drugs and risk of breast cancer recurrence. RESULTS: Our findings suggest that concurrent use of glucocorticoids, ACE inhibitors, aspirin, NSAIDs, selective COX-2 inhibitors, digoxin, and opioids has little impact on breast cancer recurrence. Similarly, patients who use SSRIs concurrently with tamoxifen treatment are not at increased risk of recurrence. In contrast, post-diagnostic use of simvastatin, a lipophilic statin, correlates with a decreased risk of breast cancer recurrence, providing a rationale for a prospective randomized clinical trial investigating simvastatin as an adjuvant therapy for breast cancer. CONCLUSION: As a whole, findings of pharmacoepidemiological studies based on DBCG data provide reassurance to physicians and healthcare personnel who provide supportive care during and after cancer (including prescriptions for comedications) and to breast cancer survivors for whom the risk of breast cancer recurrence is a major concern.
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
Progressão da Doença
Recidiva Local de Neoplasia
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos beta/uso terapêutico
Analgésicos Opioides/uso terapêutico
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico
Anti-Inflamatórios não Esteroides/uso terapêutico
Aspirina/uso terapêutico
Cardiotônicos/uso terapêutico
Inibidores de Ciclo-Oxigenase 2/uso terapêutico
Bases de Dados Factuais
Dinamarca
Digoxina/uso terapêutico
Antagonistas de Estrogênios/uso terapêutico
Feminino
Glucocorticoides/uso terapêutico
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
Inibidores da Agregação de Plaquetas/uso terapêutico
Prognóstico
Inibidores da Captação de Serotonina/uso terapêutico
Sinvastatina/uso terapêutico
Tamoxifeno/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Analgesics, Opioid); 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cardiotonic Agents); 0 (Cyclooxygenase 2 Inhibitors); 0 (Estrogen Antagonists); 0 (Glucocorticoids); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Platelet Aggregation Inhibitors); 0 (Serotonin Uptake Inhibitors); 094ZI81Y45 (Tamoxifen); 73K4184T59 (Digoxin); AGG2FN16EV (Simvastatin); R16CO5Y76E (Aspirin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1080/0284186X.2017.1407040


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[PMID]:29216640
[Au] Autor:Sun YZ; Cai N; Liu NN
[Ti] Título:Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells.
[So] Source:Cell Physiol Biochem;44(4):1640-1650, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells. METHODS: D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002). The anti-proliferative effect of celecoxib was assessed using the MTT assay. RT-PCR, Western blotting and ELISA were performed to detect the levels of PI3K, phosphorylated AKT (p-AKT), HIF-1α, VEGF and COX-2. RESULTS: Celecoxib inhibited the proliferation of RPE cells in a dose-dependent manner. Celecoxib suppressed the expression of VEGF at both the mRNA and protein levels and decreased HIF-1α protein expression. HIF-1α activation was regulated by the PI3K/AKT pathway. The celecoxib-induced down-regulation of HIF-1α and VEGF required the suppression of the hypoxia-induced PI3K/AKT pathway. However, the down-regulation of COX-2 did not occur in cells treated with celecoxib. CONCLUSIONS: The antiangiogenic effects of celecoxib in RPE cells under hypoxic conditions resulted from the inhibition of HIF-1α and VEGF expression, which may be partly mediated by a COX-2-independent, PI3K/AKT-dependent pathway.
[Mh] Termos MeSH primário: Celecoxib/farmacologia
Hipóxia Celular
Inibidores de Ciclo-Oxigenase 2/farmacologia
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Transdução de Sinais/efeitos dos fármacos
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Cromonas/farmacologia
Ciclo-Oxigenase 2/química
Ciclo-Oxigenase 2/metabolismo
Regulação para Baixo/efeitos dos fármacos
Células Epiteliais/citologia
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Morfolinas/farmacologia
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação
Proteínas Proto-Oncogênicas c-akt/metabolismo
RNA Mensageiro/metabolismo
Fator A de Crescimento do Endotélio Vascular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromones); 0 (Cyclooxygenase 2 Inhibitors); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Morpholines); 0 (RNA, Messenger); 0 (Vascular Endothelial Growth Factor A); 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one); EC 1.14.99.1 (Cyclooxygenase 2); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); JCX84Q7J1L (Celecoxib)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1159/000485764



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