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Saïd M'Dahoma, Matthieu Poitevin, Eric Dabala, Hugo Payan, Cecilia Gabriel, Elisabeth Mocaër, Sylvie Bourgoin, Michel Hamon
Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves has specific characteristics and responds differently to alleviating drugs at cephalic versus extracephalic level. This is especially true for tricyclic antidepressants currently used for alleviating neuropathic pain in humans which are less effective against cephalic neuropathic pain. Whether this also applies to the antidepressant agomelatine, with its unique pharmacological properties as MT1 /MT2 melatonin receptor agonist and 5-HT2B /5-HT2C serotonin receptor antagonist, has been investigated in two rat models of neuropathic pain...
2018: Frontiers in Pharmacology
Kazue Yoneda, Naoko Imanishi, Yoshinobu Ichiki, Fumihiro Tanaka
Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has become a "game changer" in the treatment of advanced non-small cell lung cancer (NSCLC). Its most clinically important advantage over traditional chemotherapy using cytotoxic agents are its long-term survival benefits, and some advanced NSCLC patients treated with an antibody against programmed cell death 1 (PD-1) have survived for 5 years or longer. Immune checkpoint inhibitors (ICIs) are also potentially useful for earlier-stage NSCLC when used in combination with surgery or radiotherapy...
2018: Journal of UOEH
Li Wang, Peng Wang, He Dong, Shiduan Wang, Haichen Chu, Wei Yan, Xue Zhang
Cell autophagy and cell apoptosis are both observed in the process of hypoxia-induced ischemic cerebral infarction (ICI). Unc-51 like autophagy activating kinase 1 (Ulk1) and FUN14 Domain-containing Protein 1 (FUNDC1) are both involved in the regulation of cell autophagy. This study aimed to investigate the regulatory effects of Ulk1 and FUNDC1 on hypoxia-induced nerve cell autophagy and apoptosis. Cell viability was measured using cell counting kit-8 (CCK-8) assay. Cell apoptosis was detected using Annexin V-PE/7-ADD staining assay...
June 19, 2018: Neurochemical Research
Mohsin Shah, Jean H Tayar, Noha Abdel-Wahab, Maria E Suarez-Almazor
OBJECTIVES: Immune checkpoint inhibitors (ICIs) can successfully treat cancer, but their use can be hindered by serious immune-related adverse events. We report six patients receiving ICIs who presented with de novo myositis. METHODS: We identified patients with myositis who were receiving ICIs between January 2004 and September 2016 at The University of Texas MD Anderson Cancer Center. RESULTS: Six patients developed de novo myositis. The mean age was 64...
May 18, 2018: Seminars in Arthritis and Rheumatism
M Xipell, I Victoria, V Hoffmann, J Villarreal, A García-Herrera, O Reig, L Rodas, M Blasco, E Poch, B Mellado, L F Quintana
Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues...
2018: Oncoimmunology
Osama Mohamad, Alberto Diaz de Leon, Samuel Schroeder, Andrew Leiker, Alana Christie, Elizabeth Zhang-Velten, Lakshya Trivedi, Saad Khan, Neil B Desai, Aaron Laine, Kevin Albuquerque, Puneeth Iyengar, Yull Arriaga, Kevin Courtney, David E Gerber, Hans Hammers, Hak Choy, Robert Timmerman, James Brugarolas, Raquibul Hannan
Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months...
2018: Oncoimmunology
Léa Paolini, Caroline Poli, Simon Blanchard, Thierry Urban, Anne Croué, Marie-Christine Rousselet, Sarah Le Roux, Nathalie Labarrière, Pascale Jeannin, José Hureaux
BACKGROUND: Immune checkpoint inhibitors (ICI) target T cell inhibitory pathways that are responsible for cancer tolerance by down-modulating immune functions. ICI have revolutionized patients care with lung cancer. Nevertheless, restoring endogenous antitumor T-cell responses can induce immune related adverse events, such as sarcoidosis. CASE PRESENTATION: We report here the first case of a thoracic and cutaneous sarcoid-like reaction in a patient with a relapsing unresectable non-small cell lung cancer (NSCLC) treated with nivolumab, an anti-PD-1 mAb...
June 13, 2018: Journal for Immunotherapy of Cancer
Elie El Rassy, Angela Botticella, Joseph Kattan, Cecile Le Péchoux, Benjamin Besse, Lizza Hendriks
Brain metastases (BM) are diagnosed frequently in non-small cell lung cancer (NSCLC) patients. Despite the high incidence of BM (up to 40% in unselected patients), patients with untreated and/or unstable BM were excluded from pivotal immune checkpoint inhibitors (ICI) NSCLC trials. Percentage of patients with stable and treated BM in these trials ranged from 9.1 to 14.7% and ICI benefit over chemotherapy was not always demonstrated. Only small trials have been completed that demonstrated ICI efficacy in locally untreated, selected BM patients...
May 31, 2018: Cancer Treatment Reviews
Jacob K Greenberg, Yan Yan, Christopher R Carpenter, Angela Lumba-Brown, Martin S Keller, Jose Pineda, Ross C Brownson, David Limbrick
While most children with mild TBI (mTBI) without intracranial injury (ICI) can be safely discharged home from the emergency department, many are admitted to the hospital. To support evidence-based practice, we developed a decision tool to help guide hospital admission decisions. This study was a secondary analysis of a prospective study conducted in 25 emergency departments. We included children under 18 years who had Glasgow Coma Scale score 13-15 head injuries and normal CT scans or skull fractures without significant depression...
June 8, 2018: Journal of Neurotrauma
Akifumi Tabei, Mitsuharu Watanabe, Hidekazu Ikeuchi, Masao Nakasatomi, Toru Sakairi, Yoriaki Kaneko, Akito Maeshima, Kyoichi Kaira, Junko Hirato, Yoshihisa Nojima, Keiju Hiromura
Nivolumab is an anti-programmed cell death-1 (PD-1) antibody that is utilized as an immune checkpoint inhibitor (ICI) for cancer therapy. We herein present the case of a 57-year-old man who developed acute kidney injury during treatment with nivolumab for lung cancer. A renal biopsy revealed acute tubulointerstitial nephritis. Immunohistochemical staining demonstrated marked infiltration of macrophages and T cells together with mild B cell infiltration. Of note, strong CD163+ M2 macrophage infiltration was observed...
June 6, 2018: Internal Medicine
M Kotula-Balak, P Pawlicki, A Milon, W Tworzydlo, M Sekula, A Pacwa, E Gorowska-Wojtowicz, B Bilinska, B Pawlicka, J Wiater, M Zarzycka, J Galas
In this study, G-coupled estrogen receptor (GPER) was inactivated, by treatment with antagonist (G-15), in testes of C57BL/6 mice: immature (3 weeks old), mature (3 months old) and aged (1.5 years old) (50 μg/kg bw), as well as MA-10 mouse Leydig cells (10 nM/24 h) alone or in combination with 17β-estradiol or antiestrogen (ICI 182,780). In G-15-treated mice, overgrowth of interstitial tissue was found in both mature and aged testes. Depending on age, differences in structure and distribution of various Leydig cell organelles were observed...
June 6, 2018: Cell and Tissue Research
William L Hwang, Luke R G Pike, Trevor J Royce, Brandon A Mahal, Jay S Loeffler
Immune-checkpoint inhibitors targeting cytotoxic T- lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) have transformed the care of patients with a wide range of advanced-stage malignancies. More than half of these patients will also have an indication for treatment with radiotherapy. The effects of both radiotherapy and immune-checkpoint inhibition (ICI) involve a complex interplay with the innate and adaptive immune systems, and accumulating evidence suggests that, under certain circumstances, the effects of radiotherapy synergize with those of ICI to augment the antitumour responses typically observed with either modality alone and thus improve clinical outcomes...
June 5, 2018: Nature Reviews. Clinical Oncology
Zulvikar Syambani Ulhaq, Mitsuyo Kishida
Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB), cyp19a1b , is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1) estradiol (E2 ) exposure and (2) morpholino (MO)-mediated AroB knockdown...
2018: Frontiers in Endocrinology
Ming-Xian Ho, Christina C-W Poon, Ka-Chun Wong, Zuo-Cheng Qiu, Man-Sau Wong
Genistein and icariin are flavonoid compounds that exhibit estrogen-like properties in inducing bone formation and reducing bone loss associated with estrogen deficiency in both preclinical and clinical studies. However, the mechanisms that are involved in mediating their estrogenic actions in bone cells are far from clear. The present study aimed to study the signaling pathways that mediate the estrogenic actions of genistein and icariin in osteoblastic cells. The effects of genistein and icariin on the activation of estrogen receptor (ER) and the downstream mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in murine osteoblastic MC3T3-E1 cells and rat osteoblastic UMR-106 cells were studied...
2018: Frontiers in Pharmacology
Martin P Stockli, Robert F Welton, Baoxi Han
The Spallation Neutron Source operates reliably at 1.2 MW and will gradually ramp to 1.4 MW. This paper briefly recalls some of the struggles when the unprecedented project was started and ramped to 1 MW over a 3½ year period. This was challenging, especially for the H- ion source and the low-energy beam transport system, which make up the H- injector. It took several more years to push the H- injector to the 1.4 MW requirements, and even longer to reach close to 100% injector availability. An additional breakthrough was the carefully staged, successful extension of the H- source service cycle so that disruptive source changes became rare events...
May 2018: Review of Scientific Instruments
Luigia Stefania Stucci, Stella D'Oronzo, Marco Tucci, Antonella Macerollo, Simone Ribero, Francesco Spagnolo, Elena Marra, Virginia Picasso, Laura Orgiano, Riccardo Marconcini, Francesco De Rosa, Lorenza di Guardo, Giulia Galli, Sara Gandini, Raffaele Palmirotta, Giuseppe Palmieri, Paola Queirolo, Francesco Silvestris
The role of vitamin D in melanoma is still controversial. Although several Authors described a correlation between vitamin D deficiency and poor survival in metastatic melanoma patients, clinical trials exploring the effects of vitamin D supplementation in this clinical setting were mostly inconclusive. However, recent evidence suggests that vitamin D exerts both anti-proliferative effects on tumor cells and immune-modulating activities, that have been widely explored in auto-immune disorders. On the one hand, vitamin D has been shown to inhibit T-helper17 lymphocytes, notoriously involved in the pathogenesis of immune-related adverse events (iAEs) which complicate immune-checkpoint inhibitor (ICI) treatment...
May 31, 2018: Cancer Treatment Reviews
Chi-Yung Cheng, Hsiu-Yung Pan, Chao-Jui Li, Yi-Chuan Chen, Chien-Chih Chen, Yi-Syun Huang, Fu-Jen Cheng
OBJECTIVES: Traumatic brain injury is the leading cause of death and disability in children worldwide. The objective of this study was to determine the association between physician risk tolerance and head computed tomography (CT) use in patients with minor head injury (MHI) in the emergency department (ED). METHODS: We retrospectively analyzed pediatric patients (<17 years old) with MHI in the ED and then administered 2 questionnaires (a risk-taking subscale [RTS] of the Jackson Personality Inventory and a malpractice fear scale [MFS]) to attending physicians who had evaluated these patients and made decisions regarding head CT use...
May 25, 2018: Pediatric Emergency Care
David Llopis-Castelló, Francisco Javier Camacho-Torregrosa, Alfredo García
One of every four road fatalities occurs on horizontal curves of two-lane rural roads. To this regard, many studies have been undertaken to analyze the crash risk on this road element. Most of them were based on the concept of geometric design consistency, which can be defined as how drivers' expectancies and road behavior relate. However, none of these studies included a variable which represents and estimates drivers' expectancies. This research presents a new local consistency model based on the Inertial Consistency Index (ICI)...
May 26, 2018: Accident; Analysis and Prevention
Fuling Zhou, Hui Dong, Yaling Liu, Lina Yan, Can Sun, Pengli Hao, Yuanyuan Liu, Jingxu Zhai, Yakun Liu
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease, and at present, therapies for ALS are limited. Estrogen is a potential therapeutic agent for ALS but has undesirable effects that might increase the risk of breast and uterine cancers or stroke. Raloxifene (Ral) has estrogenic properties but does not exhibit these adverse effects. However, the mechanism of Ral in ALS has not been studied. We thus investigated the effects of Ral in an NSC34 model of ALS that stably expresses the 25-kDa C-terminal fragment of TDP-43 (i...
May 25, 2018: Brain Research Bulletin
Ailin Cui, Lili Xu, Jingjing Mu, Minghui Tong, Cheng Peng, Tingting Wu
OBJECTIVE: The goal of this study was to evaluate the effect of shear wave elastography (SWE) on the measurement of rigidity changes of penile erection in venogenic erectile dysfunction (ED) and in rigidity alterations of corpus cavernosum penis with age in normal population. METHODS: The study was a prospective analysis of 81 patients referred to the department of urology with complaints of ED as well as 35 healthy volunteers. SWE was performed on the corpus cavernosum penis (CCP) in the flaccid state of healthy group...
June 2018: European Journal of Radiology
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