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https://www.readbyqxmd.com/read/27916468/design-synthesis-and-analgesic-anti-inflammatory-evaluation-of-novel-diarylthiazole-and-diarylimidazole-derivatives-towards-selective-cox-1-inhibitors-with-better-gastric-profile
#1
Ahmed H Abdelazeem, Mohammed T El-Saadi, Asmaa G Safi El-Din, Hany A Omar, Samir M El-Moghazy
The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile. Two novel series of 4,5-diarylthiazole and diarylimidazole were designed, synthesized in analogy to selective COX-1 inhibitors (mofezolac and FR122047) which lack gastric damaging effects...
November 23, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#2
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27910740/oral-squamous-cell-carcinoma-current-treatment-strategies-and-nanotechnology-based-approaches-for-prevention-and-therapy
#3
Sankalp A Gharat, Munira Momin, Chintan Bhavsar
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer; it involves damage to oral epithelial cells due to accumulation of multiple genetic mutations in the cells. OSCC remains major cause of morbidity and mortality in patients with head and neck cancers. Tobacco, smoking, alcohol consumption alone or with chewing tobacco, and betel quid are potential carcinogens contributing to the high occurrence of OSCC. Current treatment modalities for OSCC like chemoradiotherapy, surgery, EGFR inhibitors and COX-2 inhibitors, and photodynamic therapy have led to the major problems related to non-specific cell death...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27909080/ankylosing-spondylitis-versus-nonradiographic-axial-spondyloarthritis-comparison-of-tumor-necrosis-factor-inhibitor-effectiveness-and-effect-of-hla-b27-status-an-observational-cohort-study-from-the-nationwide-danbio-registry
#4
Bente Glintborg, Inge J Sørensen, Mikkel Østergaard, Lene Dreyer, Abdiweli A Mohamoud, Niels S Krogh, Oliver Hendricks, Lis S Andersen, Johnny L Raun, Marcin R Kowalski, Laura Danielsen, Randi Pelck, Henrik Nordin, Jens K Pedersen, Dorte G A Kraus, Susan R Christensen, Inger M J Hansen, Jakob Esbesen, Annette Schlemmer, Anne G Loft, Nabil Al Chaer, Lone Salomonsen, Merete L Hetland
OBJECTIVE: To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status). METHODS: Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e...
December 1, 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27908278/comparison-of-predictors-of-hip-fracture-and-mortality-after-hip-fracture-in-community-dwellers-with-and-without-alzheimer-s-disease-exposure-matched-cohort-study
#5
Anna-Maija Tolppanen, Heidi Taipale, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen
BACKGROUND: Dementia, with Alzheimer's disease (AD) being the most common form, is a major hip fracture risk factor, but currently it is not known whether the same factors predict hip fracture among persons with and without dementia/AD. We compared the predictors of hip fracture and mortality after hip fracture in persons with and without AD. METHODS: An exposure-matched cohort of all community-dwellers of Finland who received a new clinically verified AD diagnosis in 2005-2011 and had no history of previous hip fracture (N = 67,072) and an age, sex, and region-matched cohort of persons without AD (N = 67,072)...
December 1, 2016: BMC Geriatrics
https://www.readbyqxmd.com/read/27907909/egfr-kinase-inhibitors-and-gastric-acid-suppressants-in-egfr-mutant-nsclc-a-retrospective-database-analysis-of-potential-drug-interaction
#6
Nesaretnam Barr Kumarakulasinghe, Nicholas Syn, Yu Yang Soon, Atasha Asmat, Huili Zheng, En Yun Loy, Brendan Pang, Ross Andrew Soo
BACKGROUND: Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905987/factors-associated-with-the-first-antiretroviral-therapy-modification-in-older-hiv-1-positive-patients
#7
Justyna D Kowalska, Joanna Kubicka, Ewa Siwak, Piotr Pulik, Ewa Firląg-Burkacka, Andrzej Horban
BACKGROUND: Rates of first antiretroviral therapy (cART) modifications are high in most observational studies. The age-related differences in treatment duration and characteristics of first cART modifications remain underinvestigated. With increasing proportion of older patients in HIV population it is important to better understand age-related treatment effects. METHODS: Patients were included into this analysis, if being cART naïve at the first visit at the clinic...
January 7, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27901208/gastric-and-renal-effects-of-cox-2-selective-and-non-selective-nsaids-in-rats-receiving-low-dose-aspirin-therapy
#8
Marcella Goetz Moro, Paula Katherine Vargas Sanchez, Mayara Vitorino Gevert, Emeline Maria Baller, Ana Flávia Tostes, Ana Caroline Lupepsa, Sinvaldo Baglie, Gilson Cesar Nobre Franco
The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy...
November 28, 2016: Brazilian Oral Research
https://www.readbyqxmd.com/read/27900011/downregulated-microrna-26a-modulates-prostate-cancer-cell-proliferation-and-apoptosis-by-targeting-cox-2
#9
Jing Zhang, Jinghao Liang, Jianguo Huang
MicroRNA-26a (miR-26a) is expressed at lower levels in prostate cancer cells compared with normal prostate cells. However, the regulatory mechanism of miR-26a in tumorigenesis and metastasis is not clear. In the present study, the expression profile of cellular miR-26a was analyzed by reverse transcription-quantitative polymerase chain reaction. The potential target of miR-26a was identified by luciferase assay and western blotting. Examination of miR-26a function was performed by transfection with miR-26a mimics and inhibitor...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899301/role-for-nf-%C3%AE%C2%BAb-inflammatory-signalling-pathway-in-tenofovir-disoproxil-fumarate-tdf-induced-renal-damage-in-rats
#10
Hemalatha Ramamoorthy, Premila Abraham, Bina Isaac, Dhayakani Selvakumar
Nephrotoxicity due to tenofovir treatment of HIV patients has been reported. However, the mechanism of tenofovir nephrotoxicity is not clear. NFκB is an important proinflammatory transcription factor that plays a pivotal role in oxidative stress-induced inflammation. We hypothesized that NFκB proinflammatory signalling pathway may play a role in tenofovir induced renal damage. Renal damage was induced in adult male Wistar rats by the oral administration of 600 mg/kg body wt. daily for 5 consecutive weeks...
November 27, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27895738/cyclooxygenase-2-is-associated-with-malignant-phenotypes-in-human-lung-cancer
#11
Weiying Li, Wentao Yue, Hui Wang, Baitang Lai, Xuehui Yang, Chunyan Zhang, Yue Wang, Meng Gu
The objective of the present study was to investigate whether cyclooxygenase-2 (COX-2) is associated with malignancy, and to investigate its molecular mechanisms in human lung cancer tumor malignancy. The present study used RNA interference (RNAi) methodology and celecoxib, a COX-2 inhibitor, to investigate the effect of COX-2 knockdown on the proliferation and invasion abilities of lung cancer cells and the molecular mechanisms involved. Human lung adenocarcinoma A549-si10 and LTEP-A2 cells transfected with a specific small interfering RNA (A549-si10 and LTEP-A2-si10, respectively) grew more slowly compared with parental cell lines and cells transfected with pU6...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895618/cyclooxygenase-1-as-a-potential-therapeutic-target-for-seizure-suppression-evidences-from-zebrafish-pentylenetetrazole-seizure-model
#12
Patrícia Gonçalves Barbalho, Benilton de Sá Carvalho, Iscia Lopes-Cendes, Claudia Vianna Maurer-Morelli
Cyclooxygenases (COX)-1 and -2 are isoenzymes that catalyze the conversion of arachidonic acid into prostaglandins (PGs). COX-2 and PGs are rapidly increased following seizures and are known to play important roles in the neuroinflammatory process. COX-2 isoform has been predominantly explored as the most suitable target for pharmacological intervention in epilepsy studies, while COX-1 remains poorly investigated. In the present study, we evaluated the effects of selective COX-1 inhibitor or selective COX-2 inhibitor on seizure suppression in the zebrafish pentylenetetrazole (PTZ)-seizure model...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27895048/parecoxib-inhibits-glioblastoma-cell-proliferation-migration-and-invasion-by-up-regulating-mirna-29c
#13
Lin-Yong Li, Jie Xiao, Qiang Liu, Kun Xia
Glioblastoma (GBM) is one of the most lethal brain cancers worldwide, and there is an urgent need for development of novel therapeutic approaches. Parecoxib is a well-known cyclooxygenase-2 (COX-2) inhibitor, had already been developed for postoperative analgesia with high efficience and low adverse reaction. Recent study suggested that parecoxib potently enhances immunotherapeutic efficacy of GBM, but its effects on GBM growth, migration and invasion had never been studied before. In the present study, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and, BrdU (5-Bromo-2-deoxyUridine) incorporation assays were used to evaluate the cell proliferation of GBM cells...
November 28, 2016: Biology Open
https://www.readbyqxmd.com/read/27894789/cardiovascular-event-risk-assessment-in-psoriasis-patients-treated-with-tumor-necrosis-factor-%C3%AE-inhibitors-versus-methotrexate
#14
Jashin J Wu, Annie Guérin, Murali Sundaram, Katherine Dea, Martin Cloutier, Parvez Mulani
BACKGROUND: Psoriasis is associated with increased risk for cardiovascular disease. OBJECTIVE: To compare major cardiovascular event risk in psoriasis patients receiving methotrexate or tumor necrosis factor-α inhibitor (TNFi) and to assess TNFi treatment duration impact on major cardiovascular event risk. METHODS: Adult psoriasis patients with ≥2 TNFi or methotrexate prescriptions in the Truven MarketScan Databases (Q1 2000-Q3 2011) were classified as TNFi or methotrexate users...
October 26, 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27894776/design-synthesis-cyclooxygenase-inhibition-and-biological-evaluation-of-new-1-3-5-triaryl-4-5-dihydro-1h-pyrazole-derivatives-possessing-amino-methanesulfonyl-pharmacophore
#15
Khaled R A Abdellatif, Wael A A Fadaly
A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole 10a-l was designed and synthesized via cyclization of chalcones 8a-f with 4-amino/methanesulfonylphenylhydrazine hydrochloride 9a-b. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity, ulcerogenic liability and analgesic activity. All compounds were more COX-2 inhibitors than COX-1. While most compounds showed good anti-inflammatory activity, the trimethoxy derivatives (10a, 10b, 10g and 10h) were the most potent derivatives (ED50=55...
November 21, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27894402/hsp90-inhibitor-enhances-anti-proliferative-and-apoptotic-effects-of-celecoxib-on-ht-29-colorectal-cancer-cells-via-increasing-bax-bcl-2-ratio
#16
A Mohammadi, M M Yaghoobi, A GholamhoseynianNajar, B Kalantari-Khandani, H Sharifi, M Saravani
Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27894157/relationship-between-serum-infliximab-concentrations-and-risk-of-infections-in-patients-treated-for-spondyloarthritis
#17
Theodora Bejan-Angoulvant, David Ternant, Fadela Daoued, Frédéric Medina, Louis Bernard, Saloua Mammou, Gilles Paintaud, Denis Mulleman
OBJECTIVE: Tumor necrosis factor inhibitors are effective in reducing inflammation in rheumatic diseases but increase the risk of infections. This study was undertaken to investigate the relationship between the trough serum concentration of infliximab (IFX) and the risk of a first infection episode. METHODS: We retrospectively included all patients who started IFX treatment for an approved indication in our department. Patients were followed up based on recommended IFX infusion schedules...
November 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27893712/blood-vessel-endothelium-directed-tumor-cell-streaming-in-breast-tumors-requires-the-hgf-c-met-signaling-pathway
#18
E Leung, A Xue, Y Wang, P Rougerie, V P Sharma, R Eddy, D Cox, J Condeelis
During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27889951/performance-of-the-high-dimensional-propensity-score-in-a-nordic-health-care-model
#19
Jesper Hallas, Anton Pottegård
The high-dimensional propensity score (hdPS) is increasingly used as a tool to adjust for confounding in observational studies of drug effects. It was developed within very rich data sources, e.g., the American claims databases. Thus, it is unknown whether it can be applied in settings that provide little more than prescriptions and diagnoses from hospital contacts, as in the Nordic data sources. Our objective was to evaluate the performance of hdPS under such circumstances. As our model, we chose the association between use of selective cyclooxygenase-2 inhibitors (coxibs) and traditional NSAIDs (tNSAIDs) and the risk of upper GI bleeding...
November 27, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27889928/elucidating-the-role-of-cyclooxygenase-2-in-the-pathogenesis-of-oral-lichen-planus-an-immunohistochemical-study-with-supportive-histochemical-analysis
#20
Pratyush Singh, Jasleen Grover, Aditi Amit Byatnal, Vasudeva Guddattu, Raghu Radhakrishnan, Monica Charlotte Solomon
OBJECTIVE: Oral lichen planus (OLP) is a chronic, inflammatory disorder that affects the oral mucous membrane. During an inflammatory response, several chemokines and cytokines are released by the cells of the immune system. Activation of MMPs, along with mast cell-derived chymase and tryptase, degrades the basement membrane structural proteins, resulting in basement membrane breaks. AIM: To investigate the association between the COX-2 expressions, presence of intact or degranulating mast cells within the connective tissue and the extent of basement membrane discontinuity in OLP cases...
November 7, 2016: Journal of Oral Pathology & Medicine
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