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https://www.readbyqxmd.com/read/28642177/protective-functions-of-pj34-a-parp-inhibitor-is-related-to-down-regulation-of-calpain-and-nf-%C3%AE%C2%BAb-in-a-mouse-model-of-tbi
#1
Xiaogang Tao, Xuetao Chen, Zonggang Hou, Shuyu Hao, Baiyun Liu
OBJECTIVES: Poly(ADP-ribose) polymerase (PARP), calpain, and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI). METHODS: PJ34 (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally 5 min and 8 h after experimental CCI...
June 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28642034/cyclooxygenase-2-promotes-pulmonary-intravascular-macrophage-accumulation-by-exacerbating-bmp-signaling-in-rat-experimental-hepatopulmonary-syndrome
#2
Chang Liu, Jing Gao, Bing Chen, Lin Chen, Karine Belguise, Weifeng Yu, Kaizhi Lu, Xiaobo Wang, Bin Yi
BACKGROUND AND AIMS: One central factor in hepatopulmonary syndrome (HPS) pathogenesis is intravascular accumulation of activated macrophages in small pulmonary arteries. However, molecular mechanism underlyingthe macrophage accumulation in HPS is unknown. In this study, we aimed to explore whether elevated COX-2 induces the Bone morphogenicprotein-2 (BMP-2)/Crossveinless-2(CV-2) imbalance and then activation of BMP signaling pathway promotes the macrophage accumulation in Common Bile Duct Ligation (CBDL) rat lung...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28640111/comparative-safety-for-cardiovascular-outcomes-of-dpp-4-inhibitors-versus-glimepiride-in-patients-with-type-2-diabetes-a-retrospective-cohort-study
#3
Hyouk-Jun Chin, Jin Hyun Nam, Eui-Kyung Lee, Ju-Young Shin
Concerns about the cardiovascular safety of dipeptidyl peptidase-4 (DPP-4) inhibitors persist. This study sought to determine whether there is a differential risk of hospitalization for cardiovascular diseases (CVDs) between DPP-4 inhibitors and glimepiride.We conducted this retrospective cohort study by using the Korean National Health Insurance Service database from December 1, 2008, to December 31, 2013. The study subjects were new users of DPP-4 inhibitors or glimepiride for type 2 diabetes. Outcome was defined as hospitalization for CVDs, including angina pectoris, myocardial infarction, transient cerebral ischemic attack, heart failure, or cerebrovascular disease or any procedure involving coronary artery bypass grafting or percutaneous coronary intervention...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639910/apatinib-for-metastatic-breast-cancer-in-non-clinical-trial-setting-satisfying-efficacy-regardless-of-previous-anti-angiogenic-treatment
#4
Ying Lin, Zheng Wu, Jian Zhang, Xichun Hu, Zhonghua Wang, Biyun Wang, Jun Cao, Leiping Wang
Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. This study aimed to evaluate the efficacy and safety of apatinib in metastatic breast cancer (MBC) under non-clinical trial setting, and to study the impact of previous antiangiogenic treatment to the efficacy of apatinib. 52 MBC patients treated with apatinib under non-clinical trial setting in Fudan University Shanghai Cancer Center between January 1st 2015 and October 1st 2016 were included. All patients were included in time-to-treatment failure (TTF) analysis, while 45 patients were enrolled for progression-free survival (PFS) and overall survival (OS) analysis because 7 of the patients with treatment discontinuation due to intolerable toxicities had too short time for efficacy assessment...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638310/analysis-of-gene-expression-in-human-dermal-fibroblasts-treated-with-senescence-modulating-cox-inhibitors
#5
Jeong A Han, Jong-Il Kim
We have previously reported that NS-398, a cyclooxygenase-2 (COX-2)-selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2-selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment...
June 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28634425/a-transcriptional-regulatory-role-for-the-membrane-type-1-matrix-metalloproteinase-in-carcinogen-induced-inflammasome-gene-expression
#6
Samuel Sheehy, Borhane Annabi
Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28633143/tumor-associated-macrophages-in-the-development-of-4-nitroquinoline-1-oxide-induced-tongue-squamous-cell-carcinoma-in-a-mouse-model
#7
Kentaro Miki, Yorihisa Orita, Yuka Gion, Soshi Takao, Kyotaro Ohno, Mai Takeuchi, Toshihiro Ito, Akira Minoura, Tomoyasu Tachibana, Hidenori Marunaka, Takuma Makino, Akihiro Matsukawa, Kazunori Nishizaki, Tadashi Yoshino, Yasuharu Sato
OBJECTIVE: We aimed to determine the distribution of tumor-associated macrophages (TAMs) in the development of tongue squamous cell carcinoma (SCC) and to elucidate the role of TAMs in the progression of tongue SCC. METHODS: The expression of the macrophage markers nitric oxide synthase, Retnla, and mannose receptor 1 in the development of tongue SCC was longitudinally observed using real-time quantitative polymerase chain reaction. Additionally, an immunohistochemical study using an anti-mannose receptor (MR) antibody was performed...
June 21, 2017: Oncology
https://www.readbyqxmd.com/read/28632747/selective-cyclooxygenase-inhibition-by-sc-560-improves-hepatopulmonary-syndrome-in-cirrhotic-rats
#8
Ching-Chih Chang, Wen-Shin Lee, Hsian-Guey Hsieh, Chiao-Lin Chuang, Hui-Chun Huang, Fa-Yauh Lee, Shou-Dong Lee
OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by hypoxia in patients with chronic liver disease. The mechanism of HPS includes pulmonary vasodilatation, inflammation, and angiogenesis. Prostaglandins synthesized by cyclooxygenases (COX) participate in vascular responsiveness, inflammation and angiogenesis, which can be modulated by COX inhibitors. We therefore evaluated the impact of COX inhibition in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS...
2017: PloS One
https://www.readbyqxmd.com/read/28632329/postictal-hypoperfusion-hypoxia-provides-the-foundation-for-a-unified-theory-of-seizure-induced-brain-abnormalities-and-behavioral-dysfunction
#9
REVIEW
Jordan S Farrell, Roberto Colangeli, Marshal D Wolff, Alexandra K Wall, Thomas J Phillips, Antis George, Paolo Federico, G Campbell Teskey
A recent article by Farrell et al. characterizes the phenomenon, mechanisms, and treatment of a local and severe hypoperfusion/hypoxia event that occurs in brain regions following a focal seizure. Given the well-established role of cerebral ischemia/hypoxia in brain damage and behavioral dysfunction in other clinical settings (e.g., stroke, cerebral vasospasm), we put forward a new theory: postictal hypoperfusion/hypoxia is responsible for the negative consequences associated with seizures. Fortunately, inhibition of two separate molecular targets, cyclooxygenase-2 (COX-2) and l-type calcium channels, can prevent the expression of postictal hypoperfusion/hypoxia...
June 20, 2017: Epilepsia
https://www.readbyqxmd.com/read/28631191/effect-of-angiotensin-system-inhibitors-on-survival-in-newly-diagnosed-glioma-patients-and-recurrent-glioblastoma-patients-receiving-chemotherapy-and-or-bevacizumab
#10
Victor A Levin, James Chan, Meenal Datta, Jennie L Yee, Rakesh K Jain
Given prior studies that suggest the use of angiotensin system inhibitors (ASIs) is associated with prolonged overall survival (OS) in glioblastoma (GBM) patients, we evaluated the effect of ASIs in glioma patients receiving chemotherapy and/or bevacizumab (BEV). Using retrospective IRB-approved electronic chart review of newly diagnosed WHO grade 2-4 glioma patients from the Kaiser Permanente Tumor Registry of Northern California, we evaluated the impact of ASIs on OS by Cox proportional hazard model analysis for subgroups who received cytotoxic therapy, cytotoxic therapy with BEV, or BEV alone, as well as those with recurrent GBM (rGBM)...
June 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28628921/activation-of-cox-2-mpges-1-pge2-cascade-via-nlrp3-inflammasome-contributes-to-albumin-induced-proximal-tubule-cell-injury
#11
Yibo Zhuang, Fei Zhao, Jing Liang, Xu Deng, Yue Zhang, Guixia Ding, Aihua Zhang, Zhanjun Jia, Songming Huang
BACKGROUND/AIMS: The activation of NOD-like receptor family, pyrin domain containing3 (NLRP3) inflammasome has been shown to be positively correlated with the severity of proteinuria in chronic kidney disease (CKD) patients. Prostaglandin E2 (PGE2), an important inflammatory mediator, is also involved in various kidney injuries. The aim of the present study was to investigate the involvement of NLRP3 inflammasome and PGE2 synthetic pathway in albumin-induced renal tubular injury. METHODS: Murine proximal tubular cells (mPTCs) were treated with albumin to induce cell injury...
June 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28627961/microsomal-prostaglandin-e2-synthase-1-inhibitors-a-patent-review
#12
Anastasia Psarra, Aikaterini Nikolaou, Maroula G Kokotou, Dimitris Limnios, George Kokotos
Microsomal prostaglandin E2 synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) generation. It is strongly upregulated in inflamed tissues and overexpressed in tumors and it has been recognized as a key enzyme in inflammatory diseases such as arthritis, atherosclerosis, stroke and cancer. Thus, a great effort has been devoted in developing synthetic mPGES-1 inhibitors as novel anti-inflammatory agents. Areas covered: This review article summarizes the mPGES-1 inhibitors presented in patent literature from 2000 to August 2016 and their biological evaluation, discussing their activities in vitro and in vivo...
June 19, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28626213/the-efficacy-of-imrecoxib-and-celecoxib-in-axial-spondyloarthritis-and-their-influence-on-serum-dickopff-related-protein-1-dkk-1-levels
#13
Guan-Min Gao, Yan-Min Li, Xiao-Long Zheng, Dong-Bin Jiang, Lei-Lei Zhang, Peng-Hui Xu, Sheng-Yun Liu, Zhao-Hui Zheng, Quan-Cheng Kan
BACKGROUND To observe and demonstrate therapeutic effects and side effects of two selective COX-2 inhibitors, imrecoxib and celecoxib, on patients with axial spondyloarthritis (axSpA) and observe the correlation between imaging scores and serum DKK-1 levels. MATERIAL AND METHODS Sixty patients with axSpA were randomly assigned to receive 200 mg imrecoxib or 200 mg celecoxib twice daily. Fifty-one patients who completed follow-up were included in the study. At baseline, week 4, and week 12, the clinical parameters, inflammatory markers (ESR, CRP), and adverse reactions were recorded...
June 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28626088/secondary-prevention-of-cardiovascular-disease-in-patients-with-type-2-diabetes-international-insights-from-the-tecos-trial
#14
Neha J Pagidipati, Ann Marie Navar, Karen S Pieper, Jennifer B Green, M Angelyn Bethel, Paul W Armstrong, Robert G Josse, Darren K McGuire, Yuliya Lokhnygina, Jan H Cornel, Sigrun Halvorsen, Timo E Strandberg, Tuncay Delibasi, Rury R Holman, Eric D Peterson
Background -Intensive risk factor modification significantly improves outcomes for patients with diabetes and cardiovascular disease (CVD). However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. Methods -Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mmHg systolic, <90 mmHg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and non-smoking status-was evaluated among 13,616 patients from 38 countries with diabetes and known CVD at entry into TECOS...
June 16, 2017: Circulation
https://www.readbyqxmd.com/read/28625151/na-k-atpase-as-a-target-for-treatment-of-tissue-fibrosis
#15
Sergei N Orlov, Jenifer La, Larisa V Smolyaninova, Nickolai O Dulin
Myofibroblast activation is a critical process in the pathogenesis of tissue fibrosis accounting for 45% of all deaths. No effective therapies are available for the treatment of fibrotic diseases. We focus our mini-review on recent data showing that cardiotonic steroids (CTS) that are known as potent inhibitors of Na+,K+-ATPase affect myofibroblast differentiation in a cell type-specific manner. In cultured human lung fibroblasts (HLF), epithelial cells, and cancer-associated fibroblasts, CTS blocked myofibroblast differentiation triggered by profibrotic cytokine TGF-β...
June 19, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28624136/effect-of-abo-blood-type-on-the-outcomes-of-patients-with-metastatic-renal-cell-carcinoma-treated-with-first-line-tyrosine-kinase-inhibitors
#16
Kenji Omae, Shingo Fukuma, Tatsuyoshi Ikenoue, Tsunenori Kondo, Toshio Takagi, Hiroki Ishihara, Kazunari Tanabe, Shunichi Fukuhara
OBJECTIVES: To assess the effect of blood type on survival outcomes and adverse events (AEs) in patients treated with tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Patients who received TKIs as first-line therapy for mRCC between 2008 and 2015 at our hospital were included in the study (n = 136). Patients were divided into 2 groups based on their blood type as O and non-O. Survival outcomes and AEs were compared according to blood type...
June 14, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28619633/time-to-progression-after-first-line-tyrosine-kinase-inhibitor-predicts-survival-in-patients-with-metastatic-renal-cell-carcinoma-receiving-second-line-molecular-targeted-therapy
#17
Hiroki Ishihara, Tsunenori Kondo, Kazuhiko Yoshida, Kenji Omae, Toshio Takagi, Junpei Iizuka, Kazunari Tanabe
OBJECTIVES: The effect of response to first-line tyrosine kinase inhibitor (TKI) therapy on second-line survival in patients with metastatic renal cell carcinoma who receive second-line molecular-targeted therapy (mTT) after first-line failure remains unclear. MATERIALS AND METHODS: Sixty patients who developed disease progression after first-line TKI, without prior cytokine therapy, were enrolled. According to the median first-line time to progression (1L-TTP), patients were divided into 2 groups (i...
June 12, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28618947/treatment-outcome-comparisons-between-exons-19-and-21-egfr-mutations-for-non-small-cell-lung-cancer-patients-with-malignant-pleural-effusion-after-first-line-and-second-line-tyrosine-kinase-inhibitors
#18
Zhen Zheng, Deyao Xie, Huafang Su, Baochai Lin, Lihao Zhao, Xia Deng, Hanbin Chen, Shaoran Fei, Xiance Jin, Congying Xie
Recent studies demonstrated a significantly increased frequency of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions (MPEs). The purpose of this study is to investigate the effect of first-line and second-line EGFR-tyrosine kinase inhibitors (TKIs) in the treatment of NSCLC with MPEs harboring exon 19 deletion and L858R mutation. From 2010 to 2015, 203 NSCLC patients with MPEs harboring EGFR mutation treated with EGFR-TKIs were reviewed...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28614595/perioperative-cox-2-inhibitors-may-increase-the-risk-of-post-operative-acute-kidney-injury
#19
A Abrahamsson, J Oras, J Snygg, L Block
BACKGROUND: In enhanced recovery protocols (ERP), a restrictive fluid regimen is proposed. Patients who undergo major surgery have an increased risk of post-operative acute kidney injury (AKI). This combination may pose difficulties when ERP is used for patients undergoing major surgery. The aim of this study was to evaluate whether patients undergoing pancreatic surgery and treated with a restrictive fluid regimen are at greater risk of post-operative AKI. Furthermore, if there was an increased risk of AKI, we aimed to identify its cause...
June 14, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28611669/cd24-expression-is-increased-in-5-fluorouracil-treated-esophageal-adenocarcinoma-cells
#20
Pilar Jiménez, Eduardo Chueca, María Arruebo, Mark Strunk, Estela Solanas, Trinidad Serrano, María A García-González, Ángel Lanas
The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor...
2017: Frontiers in Pharmacology
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