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Frontiers in Pharmacology

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https://www.readbyqxmd.com/read/29773991/first-biologic-drug-in-the-treatment-of-ras-wild-type-metastatic-colorectal-cancer-anti-egfr-or-bevacizumab-results-from-a-meta-analysis
#1
REVIEW
Alessandro Ottaiano, Alfonso De Stefano, Monica Capozzi, Anna Nappi, Chiara De Divitiis, Carmela Romano, Lucrezia Silvestro, Antonino Cassata, Rossana Casaretti, Salvatore Tafuto, Michele Caraglia, Massimiliano Berretta, Guglielmo Nasti, Antonio Avallone
Introduction: We performed a meta-analysis in order to analyze and quantify the effect on survival of starting therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC) patients with anti-EGFR agents or bevacizumab. Patients and Methods: Randomized, phase II or III, clinical trials reporting overall survival (OS) in RAS wt mCRC patients treated with first-line chemotherapy (CT) associated with bevacizumab or anti-EGFR agents were selected. The primary end-point of this meta-analysis was OS; findings were depicted in classical Forest plots...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773990/atorvastatin-inhibits-inflammatory-response-attenuates-lipid-deposition-and-improves-the-stability-of-vulnerable-atherosclerotic-plaques-by-modulating-autophagy
#2
Shi Peng, Long-Wei Xu, Xin-Yu Che, Qing-Qing Xiao, Jun Pu, Qin Shao, Ben He
Atherosclerosis is a chronic disease comprising intima malfunction and arterial inflammation. Recent studies have demonstrated that autophagy could inhibit inflammatory response in atherosclerosis and exert subsequent atheroprotective effects. Our previous study also demonstrated the role of autophagy in the inhibition of inflammation by atorvastatin in vitro . Therefore, in the present study, we aimed to determine whether atorvastatin could upregulate autophagy to inhibit inflammatory cytokines secretion, lipid accumulation, and improve vulnerable plaque stability, both in vitro and in vivo ...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773989/the-cytotoxic-effects-of-betulin-conjugated-gold-nanoparticles-as-stable-formulations-in-normal-and-melanoma-cells
#3
Marius Mioc, Ioana Zinuca Pavel, Roxana Ghiulai, Dorina E Coricovac, Claudia Farcaş, Ciprian-Valentin Mihali, Camelia Oprean, Vlad Serafim, Ramona A Popovici, Cristina A Dehelean, Michael I Shtilman, Aristidis M Tsatsakis, Codruţa Şoica
Gold nanoparticles are currently investigated as theranostics tools in cancer therapy due to their proper biocompatibility and increased efficacy related to the ease to customize the surface properties and to conjugate other molecules. Betulin, [lup-20(29)-ene-3β, 28-diol], is a pentacyclic triterpene that has raised scientific interest due to its antiproliferative effect on several cancer types. Herein we described the synthesis of surface modified betulin-conjugated gold nanoparticles using a slightly modified Turkevich method...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773988/microglia-p2y-13-receptors-prevent-astrocyte-proliferation-mediated-by-p2y-1-receptors
#4
Clara Quintas, Nuno Vale, Jorge Gonçalves, Glória Queiroz
Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773987/celastrol-attenuates-the-invasion-and-migration-and-augments-the-anticancer-effects-of-bortezomib-in-a-xenograft-mouse-model-of-multiple-myeloma
#5
Muthu K Shanmugam, Kwang S Ahn, Jong H Lee, Radhamani Kannaiyan, Nurulhuda Mustafa, Kanjoormana A Manu, Kodappully S Siveen, Gautam Sethi, Wee J Chng, Alan P Kumar
Several lines of evidence have demonstrated that deregulated activation of NF-κB plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-κB upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated. In addition, we studied whether CSL can potentiate the apoptotic effect of bortezomib, a proteasome inhibitor in MM cells and in a xenograft mouse model...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773986/flavopiridol-protects-bone-tissue-by-attenuating-rankl-induced-osteoclast-formation
#6
Zi'ang Hu, Yilei Chen, Lijiang Song, Jasper H N Yik, Dominik R Haudenschild, Shunwu Fan
Bone resorption and homeostasis is carried out by osteoclasts, whose differentiation and activity are regulated by the RANK/RANKL axis. Our previous studies using a mouse model of joint injury show that joint trauma induces local inflammation followed by bone remodeling. The transcription factor cyclin-dependent kinase 9 (CDK9) is the major regulator of inflammation, as CDK9 inhibitor flavopiridol effectively suppress injury-induced inflammatory response. The objective of this study was to investigate the underlying mechanism through which flavopiridol regulates bone resorption...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29770114/extracts-of-artocarpus-communis-induce-mitochondria-associated-apoptosis-via-pro-oxidative-activity-in-human-glioblastoma-cells
#7
Chiang-Wen Lee, Lee-Fen Hsu, Ming-Hsueh Lee, I-Ta Lee, Ju-Fang Liu, Yao-Chang Chiang, Ming-Horng Tsai
Glioblastoma multiforme (GBM) is an extremely aggressive and devastating malignant tumor in the central nervous system. Its incidence is increasing and the prognosis is poor. Artocarpin is a natural prenylated flavonoid with various anti-inflammatory and anti-tumor properties. Studies have shown that artocarpin is associated with cell death of primary glioblastoma cells. However, the in vivo effects and the cellular and molecular mechanisms modulating the anticancer activities of artocarpin remain unknown. In this study, we demonstrated that treating the glioblastoma cell lines U87 and U118 cells with artocarpin induced apoptosis...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765326/descriptions-of-adverse-drug-reactions-are-less-informative-in-forums-than-in-the-french-pharmacovigilance-database-but-provide-more-unexpected-reactions
#8
Pierre Karapetiantz, Florelle Bellet, Bissan Audeh, Jérémy Lardon, Damien Leprovost, Rim Aboukhamis, François Morlane-Hondère, Cyril Grouin, Anita Burgun, Sandrine Katsahian, Marie-Christine Jaulent, Marie-Noëlle Beyens, Agnès Lillo-Le Louët, Cédric Bousquet
Background: Social media have drawn attention for their potential use in Pharmacovigilance. Recent work showed that it is possible to extract information concerning adverse drug reactions (ADRs) from posts in social media. The main objective of the Vigi4MED project was to evaluate the relevance and quality of the information shared by patients on web forums about drug safety and its potential utility for pharmacovigilance. Methods: After selecting websites of interest, we manually evaluated the relevance of the content of posts for pharmacovigilance related to six drugs (agomelatine, baclofen, duloxetine, exenatide, strontium ranelate, and tetrazepam)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765325/mequindox-induced-kidney-toxicity-is-associated-with-oxidative-stress-and-apoptosis-in-the-mouse
#9
Qianying Liu, Zhixin Lei, Jingchao Guo, Aimei Liu, Qirong Lu, Zainab Fatima, Haseeb Khaliq, Muhammad A B Shabbir, Muhammad Kashif Maan, Qinghua Wu, Menghong Dai, Xu Wang, Yuanhu Pan, Zonghui Yuan
Mequindox (MEQ), belonging to quinoxaline-di- N -oxides (QdNOs), is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765324/evodiamine-a-novel-notch3-methylation-stimulator-significantly-suppresses-lung-carcinogenesis-in-vitro-and-in-vivo
#10
Tao Su, Xia Yang, Jian-Hua Deng, Qiu-Ju Huang, Su-Chao Huang, Yan-Min Zhang, Hong-Ming Zheng, Ying Wang, Lin-Lin Lu, Zhong-Qiu Liu
Lung cancer is a leading cause of cancer-related deaths worldwide. NOTCH3 signaling is mainly expressed in non-small cell lung carcinoma (NSCLC), and has been proposed as a therapeutic target of NSCLC. While, few agents for preventing or treating NSCLC via targeting NOTCH3 signaling are used in modern clinical practice. Evodiamine (EVO), an alkaloid derived from Euodiae Fructus, possesses low toxicity and has long been shown to exert anti-lung cancer activity. However, the underlying anti-lung cancer mechanisms of EVO are not yet fully understood...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765323/up-down-reader-an-open-source-program-for-efficiently-processing-50-von-frey-thresholds
#11
Rafael Gonzalez-Cano, Bruno Boivin, Daniel Bullock, Laura Cornelissen, Nick Andrews, Michael Costigan
Most pathological pain conditions in patients and rodent pain models result in marked alterations in mechanosensation and the gold standard way to measure this is by use of von Frey fibers. These graded monofilaments are used to gauge the level of stimulus-evoked sensitivity present in the affected dermal region. One of the most popular methods used to determine von Frey thresholds is the up-down testing paradigm introduced by Dixon for patients in 1980 and by Chapman and colleagues for rodents in 1994. Although the up-down method is very accurate, leading to its widespread use, defining the 50% threshold from primary data is complex and requires a relatively time-consuming analysis step...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765322/therapeutic-potential-of-ginsenosides-as-an-adjuvant-treatment-for-diabetes
#12
REVIEW
Litao Bai, Jialiang Gao, Fan Wei, Jing Zhao, Danwei Wang, Junping Wei
Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765321/brain-lipopolysaccharide-preconditioning-induced-gene-reprogramming-mediates-a-tolerance-state-in-electroconvulsive-shock-model-of-epilepsy
#13
Elham Amini, Mojtaba Golpich, Abdoreza S Farjam, Behnam Kamalidehghan, Zahurin Mohamed, Norlinah M Ibrahim, Abolhassan Ahmadiani, Azman A Raymond
There is increasing evidence pointing toward the role of inflammatory processes in epileptic seizures, and reciprocally, prolonged seizures induce more inflammation in the brain. In this regard, effective strategies to control epilepsy resulting from neuroinflammation could be targeted. Based on the available data, preconditioning (PC) with low dose lipopolysaccharide (LPS) through the regulation of the TLR4 signaling pathway provides neuroprotection against subsequent challenge with injury in the brain. To test this, we examined the effects of a single and chronic brain LPS PC, which is expected to lead to reduction of inflammation against epileptic seizures induced by electroconvulsive shock (ECS)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765320/distinct-analgesic-actions-of-dha-and-dha-derived-specialized-pro-resolving-mediators-on-post-operative-pain-after-bone-fracture-in-mice
#14
Linlin Zhang, Niccolò Terrando, Zhen-Zhong Xu, Sangsu Bang, Sven-Eric Jordt, William Maixner, Charles N Serhan, Ru-Rong Ji
Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs), derived from fish oil docosahexaenoic acid (DHA), promote the resolution of acute inflammation and potently inhibit inflammatory and neuropathic pain. In this study, we examined the analgesic impact of DHA and DHA-derived SPMs in a mouse model of post-operative pain induced by tibial bone fracture (fPOP). Intravenous perioperative treatment with DHA (500 μg), resolvin D1 (RvD1, 500 ng) and maresin 1 (MaR1, 500 ng), 10 min and 24 h after the surgery, delayed the development of fPOP (mechanical allodynia and cold allodynia)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765319/progression-and-regression-of-hepatic-lesions-in-a-mouse-model-of-nash-induced-by-dietary-intervention-and-its-implications-in-pharmacotherapy
#15
Zhi-Ming Ding, Yue Xiao, Xikun Wu, Haixia Zou, Shurong Yang, Yiyun Shen, Juehua Xu, Heather C Workman, Amy L Usborne, Haiqing Hua
Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765318/utility-of-a-novel-three-dimensional-and-dynamic-3dd-cell-culture-system-for-pk-pd-studies-evaluation-of-a-triple-combination-therapy-at-overcoming-anti-her2-treatment-resistance-in-breast-cancer
#16
Anusha Ande, Tanaya R Vaidya, Bao N Tran, Michael Vicchiarelli, Ashley N Brown, Sihem Ait-Oudhia
Background: Emergence of Human epidermal growth factor receptor 2 (HER2) therapy resistance in HER2-positive (HER2+) breast cancer (BC) poses a major clinical challenge. Mechanisms of resistance include the over-activation of the PI3K/mTOR and Src pathways. This work aims to investigate a novel combination therapy that employs paclitaxel (PAC), a mitotic inhibitor, with everolimus (EVE), an mTOR inhibitor, and dasatinib (DAS), an Src kinase inhibitor, as a modality to overcome resistance. Methods: Static (two dimensional, 2D) and three-dimensional dynamic (3DD) cell culture studies were conducted using JIMT-1 cells, a HER2+ BC cell line refractory to HER2 therapies...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765317/sodium-tanshinone-iia-sulfonate-decreases-cigarette-smoke-induced-inflammation-and-oxidative-stress-via-blocking-the-activation-of-mapk-hif-1%C3%AE-signaling-pathway
#17
Ruijuan Guan, Jian Wang, Ziying Li, Mingjing Ding, Defu Li, Guihua Xu, Tao Wang, Yuqin Chen, Qian Yang, Zhen Long, Zhou Cai, Chenting Zhang, Xue Liang, Lian Dong, Li Zhao, Haiyun Zhang, Dejun Sun, Wenju Lu
Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α-induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29760662/targeting-renin-angiotensin-system-against-alzheimer-s-disease
#18
REVIEW
Abadi Kahsu Gebre, Birhanetensay Masresha Altaye, Tesfay Mehari Atey, Kald Beshir Tuem, Derbew Fikadu Berhe
Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29760661/a-semantic-transformation-methodology-for-the-secondary-use-of-observational-healthcare-data-in-postmarketing-safety-studies
#19
Anil Pacaci, Suat Gonul, A Anil Sinaci, Mustafa Yuksel, Gokce B Laleci Erturkmen
Background: Utilization of the available observational healthcare datasets is key to complement and strengthen the postmarketing safety studies. Use of common data models (CDM) is the predominant approach in order to enable large scale systematic analyses on disparate data models and vocabularies. Current CDM transformation practices depend on proprietarily developed Extract-Transform-Load (ETL) procedures, which require knowledge both on the semantics and technical characteristics of the source datasets and target CDM...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29760660/ophiopogonin-d-a-natural-product-from-radix-ophiopogonis-induces-in-vitro-and-in-vivo-ripk1-dependent-and-caspase-independent-apoptotic-death-in-androgen-independent-human-prostate-cancer-cells
#20
Zongliang Lu, He Wang, Mingxing Zhu, Wei Song, Jiajia Wang, Changpeng Wu, Ya Kong, Jing Guo, Na Li, Jie Liu, Yanwu Li, Hongxia Xu
Objective: The purpose of this study was to evaluate the anticancer effects of Ophiopogonin D' (OPD', a natural product extracted from a traditional Chinese medicine ( Radix Ophiopogonis ) against androgen-independent prostate cancer cells and to explore the underlying molecular mechanism(s) of action. Methods: The CCK-8 assay was used to assess the viability of prostate cancer cells. The cell morphology was examined by an ultrastructural analysis via transmission electron microscopy. Cells in apoptosis (early and late stages) were detected using an Annexin V-FITC/propidium iodide kit with a FACSCaliber flow cytometer...
2018: Frontiers in Pharmacology
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