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https://www.readbyqxmd.com/read/28646772/prevalence-of-immune-related-systemic-adverse-events-in%C3%A2-patients-treated-with-anti-programmed-cell-death-1-anti-programmed-cell-death-ligand-1-agents-a-single-centre-pharmacovigilance-database-analysis
#1
Sébastien Le Burel, Stéphane Champiat, Christine Mateus, Aurélien Marabelle, Jean-Marie Michot, Caroline Robert, Rakiba Belkhir, Jean-Charles Soria, Salim Laghouati, Anne-Laure Voisin, Olivier Fain, Arsène Mékinian, Laetitia Coutte, Tali-Anne Szwebel, Laetitia Dunogeant, Bertrand Lioger, Cécile Luxembourger, Xavier Mariette, Olivier Lambotte
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)(1) a French registry of grade ≥2 irAEs occurring in ICI-treated patients...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28645491/systematic-review-of-immune-checkpoint-inhibition-in-urological-cancers
#2
REVIEW
Maud Rijnders, Ronald de Wit, Joost L Boormans, Martijn P J Lolkema, Astrid A M van der Veldt
CONTEXT: In patients with advanced and metastatic urological cancers, clinical outcome may be improved by immune checkpoint inhibitors (ICIs). OBJECTIVE: To systematically review relevant literature on efficacy and safety of ICIs in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. EVIDENCE ACQUISITION: Relevant databases, including Medline, Embase, and the Cochrane Library, were searched up to March 16, 2017...
June 20, 2017: European Urology
https://www.readbyqxmd.com/read/28640977/neurogenic-bowel-dysfunction-clinical-management-recommendations-of-the-neurologic-incontinence-committee-of-the-fifth-international-consultation-on-incontinence-2013
#3
REVIEW
Nikki Cotterill, Helmut Madersbacher, Jean J Wyndaele, Apostolos Apostolidis, Marcus J Drake, Jerzy Gajewski, John Heesakkers, Jalesh Panicker, Piotr Radziszewski, Ryuji Sakakibara, Karl-Dietrich Sievert, Rizwan Hamid, Thomas M Kessler, Anton Emmanuel
BACKGROUND: Evidence-based guidelines for the management of neurological disease and lower bowel dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. AIMS: To update clinical management of neurogenic bowel dysfunction from the recommendations of the 4th ICI, 2009. MATERIALS AND METHODS: A series of evidence reviews and updates were performed by members of the working group...
June 22, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28633868/daidzein-stimulates-osteogenesis-facilitating-proliferation-differentiation-and-antiapoptosis-in-human-osteoblast-like-mg-63-cells-via-estrogen-receptor-dependent-mek-erk-and-pi3k-akt-activation
#4
Xin Jin, Jing Sun, Bo Yu, Yue Wang, Wei Jia Sun, Jing Yang, Su Hui Huang, Wen Li Xie
Daidzein, a natural soy isoflavone, has a structure similar to estradiol and exhibiting bone-sparing effects against osteoporosis. However, the molecular mechanisms of osteogenesis remain unclear. We hypothesized that daidzein stimulates osteogenesis through estrogen receptor (ER)-dependent signal pathways. To test this hypothesis, we investigated the effects of daidzein compared with 17β-estradiol on proliferation, differentiation, and cisplatin-induced apoptosis in human osteoblast-like MG-63 cells containing 2 ER isoforms...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28631811/the-effects-of-fat-structures-and-ice-cream-mix-viscosity-on-physical-and-sensory-properties-of-ice-cream
#5
Julia Amador, Rich Hartel, Scott Rankin
The purpose of this work was to investigate iciness perception and other sensory textural attributes of ice cream due to ice and fat structures and mix viscosity. Two studies were carried out varying processing conditions and mix formulation. In the 1st study, ice creams were collected at -3, -5, and -7.5 °C draw temperatures. These ice creams contained 0%, 0.1%, or 0.2% emulsifier, an 80:20 blend of mono- and diglycerides: polysorbate 80. In the 2nd study, ice creams were collected at -3 °C draw temperature and contained 0%, 0...
June 20, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28627387/observational-fear-learning-in-degus-is-correlated-with-temporal-vocalization-patterns
#6
Navdeep Lidhar, Nathan Insel, June Yue Dong, Kaori Takehara-Nishiuchi
Some animals learn to fear a situation after observing another individual come to harm, and this learning is influenced by the animals' social relationship and history. An important but sometimes overlooked factor in studies of observational fear learning is that social context not only affects observers, but may also influence the behavior and communications expressed by those being observed. Here we sought to investigate whether observational fear learning in the degu (Octodon degus) is affected by social familiarity, and the degree to which vocal expressions of alarm or distress contribute...
June 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28622628/limitations-and-opportunities-for-immune-checkpoint-inhibitors-in-pediatric-malignancies
#7
REVIEW
Jeong A Park, Nai-Kong V Cheung
Immune checkpoint inhibitors (ICI) have shown great promise in a wide spectrum of adult solid and hematological malignancies, achieving objective tumor responses and prolonging survival. However, there is limited clinical success amongst pediatric patients. In this review, we summarize the current understanding of ICI and present an up-to-date overview of recent and ongoing clinical trials of ICI in pediatric malignancies. In addition, we will discuss immunologic and clinical difficulties in this young population, as well as future prospects for combination of ICI with other immune-based and conventional treatments...
June 1, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28620681/cardiac-t1-mapping-in-congenital-heart-disease-bolus-vs-infusion-protocols-for-measurements-of-myocardial-extracellular-volume-fraction
#8
Nadya Al-Wakeel-Marquard, Sanaz Rastin, Frédéric Muench, Darach O H-Ici, Sevim Yilmaz, Felix Berger, Titus Kuehne, Daniel R Messroghli
Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD)...
June 15, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28618207/effect-of-dioxin-and-17%C3%AE-estradiol-on-the-expression-of-cytochrome-p450-1a1-gene-via-an-estrogen-receptor-dependent-pathway-in-cellular-and-xenografted-models
#9
Ryeo-Eun Go, Kyung-A Hwang, Cho-Won Kim, Yong-Sub Byun, Ki-Hoan Nam, Kyung-Chul Choi
Cytochrome P450 (CYP) 1A1 plays a major role in the metabolic activation of procarcinogens to carcinogens via aryl hydrocarbon receptor (AhR) pathway. Especially, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known as an agonist of AhR. In estrogen responsive cancers, 17β-estradiol (E2) may influence on AhR dependent expression of CYP1 family via the interaction between estrogen receptor (ER) and AhR. In the present study, the effect of E2/ER on the expression of AhR and CYP1A1 genes was investigated for MCF-7 clonal variant (MCF-7 CV) breast cancer cells expressing ER...
June 15, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28615727/oestrogen-inhibits-arterial-calcification-by-promoting-autophagy
#10
Yi-Qun Peng, Dan Xiong, Xiao Lin, Rong-Rong Cui, Feng Xu, Jia-Yu Zhong, Ting Zhu, Feng Wu, Min-Zhi Mao, Xiao-Bo Liao, Ling-Qing Yuan
Arterial calcification is a major complication of cardiovascular disease. Oestrogen replacement therapy in postmenopausal women is associated with lower levels of coronary artery calcification, but its mechanism of action remains unclear. Here, we show that oestrogen inhibits the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) in vitro and arterial calcification in vivo by promoting autophagy. Through electron microscopy, GFP-LC3 redistribution, and immunofluorescence analyses as well as measurement of the expression of the autophagosome marker light-chain I/II (LC3I/II) and autophagy protein 5 (Atg5), we show that autophagy is increased in VSMCs by oestrogen in vitro and in vivo...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610825/integrating-next-generation-dendritic-cell-vaccines-into-the-current-cancer-immunotherapy-landscape
#11
REVIEW
Abhishek D Garg, Pierre G Coulie, Benoit J Van den Eynde, Patrizia Agostinis
Cancer immunotherapy is experiencing a renaissance spearheaded by immune checkpoint inhibitors (ICIs). This has spurred interest in 'upgrading' existing immunotherapies that previously experienced only sporadic success, such as dendritic cells (DCs) vaccines. In this review, we discuss the major molecular, immunological, and clinical determinants of existing first- and second-generation DC vaccines. We also outline the future trends for next-generation DC vaccines and describe their major hallmarks and prerequisites necessary for high anticancer efficacy...
June 10, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28607424/benzo-a-pyrene-triggers-desensitization-of-%C3%AE-2-adrenergic-pathway
#12
Abdullah Mayati, Normand Podechard, Manuelle Rineau, Lydie Sparfel, Dominique Lagadic-Gossmann, Olivier Fardel, Eric Le Ferrec
Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B(a)P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that B(a)P can directly interact with the β2ADR, we investigated here whether B(a)P could decrease β2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a)P reduced β2ADR-mediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28603032/%C3%AE-2-adrenergic-receptor-mediated-in-vitro-regulation-of-human-hepatic-drug-transporter-expression-by-epinephrine
#13
Abdullah Mayati, Amélie Moreau, Claire Denizot, Bruno Stieger, Yannick Parmentier, Olivier Fardel
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10μM epinephrine for 24h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP...
June 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28601879/outcomes-in-melanoma-patients-treated-with-braf-mek-directed-therapy-or-immune-checkpoint-inhibition-stratified-by-clinical-trial-versus-standard-of-care
#14
Chloe Goldman, Jeremy Tchack, Eric M Robinson, Sung Won Han, Una Moran, David Polsky, Russell S Berman, Richard L Shapiro, Patrick A Ott, Iman Osman, Hua Zhong, Anna C Pavlick, Melissa Ann Wilson
OBJECTIVES: Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population...
June 10, 2017: Oncology
https://www.readbyqxmd.com/read/28600350/rheumatoid-arthritis-and-polymyalgia-rheumatica-occurring-after-immune-checkpoint-inhibitor-treatment
#15
Rakiba Belkhir, Sébastien Le Burel, Laetitia Dunogeant, Aurélien Marabelle, Antoine Hollebecque, Benjamin Besse, Alexandra Leary, Anne-Laure Voisin, Clémence Pontoizeau, Laetitia Coutte, Edouard Pertuiset, Gaël Mouterde, Olivier Fain, Olivier Lambotte, Xavier Mariette
OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment. METHODS: This was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR...
June 9, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28591870/transcriptome-profiling-reveals-bisphenol-a-alternatives-activate-estrogen-receptor-alpha-in-human-breast-cancer-cells
#16
Robin Mesnage, Alexia Phedonos, Matthew Arno, Sucharitha Balu, J Christopher Corton, Michael N Antoniou
Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in "BPA-free" products. We have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines. Estrogenicity was assessed (10-11M to 10-4M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay...
June 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28588484/akrinor-tm-a-cafedrine-theodrenaline-mixture-20-1-increases-force-of-contraction-of-human-atrial-myocardium-but-does-not-constrict-internal-mammary-artery-in-vitro
#17
Benjamin Kloth, Simon Pecha, Eileen Moritz, Yvonne Schneeberger, Klaus-Dieter Söhren, Edzard Schwedhelm, Hermann Reichenspurner, Thomas Eschenhagen, Rainer H Böger, Torsten Christ, Sebastian N Stehr
Background: Intraoperative hypotension is a common problem and direct or indirect sympathomimetic drugs are frequently needed to stabilize blood pressure. Akrinor(TM) consists of the direct and the indirect sympathomimetic noradrenaline and norephedrine. Both substances are covalently bound to the phosphodiesterase (PDE) inhibitor theophylline, yielding theodrenaline and cafedrine, respectively. We investigated pharmacodynamic effects of Akrinor(TM) and its constituents on contractile force and tension in human atrial trabeculae and internal A...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28586025/protective-role-of-17%C3%AE-estradiol-on-tumor-necrosis-factor-%C3%AE-induced-apoptosis-in-human-nucleus-pulposus-cells
#18
Huan Liu, Si-Dong Yang, Ying Xu, Sheng-Hua Ning, Tao Wang, Da-Long Yang, Wen-Yuan Ding
The molecular mechanisms underlying protection and pathogenesis in spinal degenerative diseases remain unclear. Tumor necrosis factor-α (TNF-α) has been demonstrated to induce apoptosis of inte rvertebral disc (IVD) cells during IVD degeneration, and 17β‑estradiol (17β‑E2) has a protective effect against IVD cell apoptosis. However, the underlying molecular mechanism by which 17β‑E2 protects nucleus pulposus (NP) cells remains to be investigated. The aim of the present study was to evaluate whether 17β‑E2 modulates apoptosis of human NP cells induced by TNF‑α...
June 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28586020/altered-expression-of-epithelial-mesenchymal-transition-and-pluripotent-associated-markers-by-sex-steroid-hormones-in-human-embryonic-stem-cells
#19
So-Ye Jeon, Kyung-A Hwang, Cho-Won Kim, Eui-Bae Jeung, Kyung-Chul Choi
Embryonic stem (ES) cells are pluripotent stem cells derived from a developmental stage of pre‑implanted embryos. The present study investigated the effect of female sex steroid hormones on the characteristics of human ES cells by using a feeder‑free culture protocol. In a feeder‑free condition without sex hormones, human ES cells assumed the form of tightly packed cells that grow in a monolayer. The cells had clean and defined edges with no evidence of differentiation and expressed several markers specific for undifferentiated ES cells including POU class 5 homeobox 1 (POU5F1), sex determining region Y‑box 2 (SOX2) and NANOG homeobox (NANOG)...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28585612/-recent-advances-of-immunooncology-in-the-treatment-of-solid-tumours-and-haematological-malignancies-the-immune-checkpoint-inhibitors
#20
Viktória Fésüs
Cancer immunotherapy is coming of age, as outstanding results can be achieved in the therapy of cancer with poor prognosis by altering the patients' immune system and by promoting the immune response against tumours. Amongst immunotherapies, the immune checkpoint inhibitors (ICI) proved to be the most effective, primarily in the treatment of solid tumours, including melanoma, non-small cell lung carcinoma, and classical Hodgkin's lymphoma. The reason for this efficacy is the immunosuppressive microenvironment typical for many cancer types, directly and indirectly inhibiting effector T-cell responses...
June 6, 2017: Magyar Onkologia
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