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https://www.readbyqxmd.com/read/28731496/prognostic-factors-for-survival-in-metastatic-renal-cell-carcinoma-patients-with-brain-metastases-receiving-targeted-therapy
#1
Ibrahim Yildiz, Ahmet Bilici, Nuri Karadurmuş, Leyla Ozer, Deniz Tural, Mehmet A Kaplan, Tülay Akman, Ibrahim V Bayoglu, Mükremin Uysal, Yaşar Yildiz, Özgür Tanriverdi, Ozan Yazici, Zeki Sürmeli, Nazim Serdar Turhal, Sevil Bavbek, Fatih Selçukbiricik, Doğan Koca, Mert Basaran
BACKGROUND: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. PATIENTS AND METHODS: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. RESULTS: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70...
July 14, 2017: Tumori
https://www.readbyqxmd.com/read/28725915/ikk%C3%AE-inhibition-prevents-fat-induced-beta-cell-dysfunction-in-vitro-and-in-vivo-in-rodents
#2
Aleksandar Ivovic, Andrei I Oprescu, Khajag Koulajian, Yusaku Mori, Judith A Eversley, Liling Zhang, Rodolfo Nino-Fong, Gary F Lewis, Marc Y Donath, Michael Karin, Michael B Wheeler, Jan Ehses, Allen Volchuk, Catherine B Chan, Adria Giacca
AIMS/HYPOTHESIS: We have previously shown that oxidative stress plays a causal role in beta cell dysfunction induced by fat. Here, we address whether the proinflammatory kinase inhibitor of (nuclear factor) κB kinase β (IKKβ), which is activated by oxidative stress, is also implicated. METHODS: Fat (oleate or olive oil) was infused intravenously in Wistar rats for 48 h with or without the IKKβ inhibitor salicylate. Thereafter, beta cell function was evaluated in vivo using hyperglycaemic clamps or ex vivo in islets isolated from fat-treated rats...
July 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28722266/second-generation-drug-eluting-stents-versus-bare-metal-stents-for-percutaneous-coronary-intervention-of-the-proximal-left-anterior-descending-artery-an-analysis-of-the-basket-prove-i-and-ii-trials
#3
Fernanda Marinho Mangione, Tor Biering-Sørensen, Kotaro Nochioka, Tannas Jatene, Odilson Marcos Silvestre, Kim Wadt Hansen, Rikke Sørensen, Jan Skov Jensen, Peter Godsk Jorgensen, Raban Jeger, Christoph Kaiser, Matthias Pfisterer, Søren Galatius
OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to be safe options for the treatment of proximal LAD stenosis, however associated with considerable reintervention rates. Overall, second-generation DES has proven to be superior to BMS and first-generation DES, nevertheless, its effect for proximal LAD PCI has not previously been reported...
July 19, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28722023/potential-involvement-of-impaired-bkca-channel-function-in-sensory-defensiveness-and-some-behavioral-disturbances-induced-by-unfamiliar-environment-in-a-mouse-model-of-fxs
#4
Maria Isabel Carreno-Munoz, Fabienne Martins, Maria Carmen Medrano, Elisabetta Aloisi, Susanna Pietropaolo, Corentin Dechaud, Enejda Subashi, Guillaume Bony, Melanie Ginger, Abdelmalik Moujahid, Andreas Frick, Xavier Leinekugel
In Fragile X Syndrome (FXS), sensory-hypersensitivity and impaired habituation is thought to result in attention overload and various behavioral abnormalities in reaction to the excessive and remanent salience of environment-features that would normally be ignored. This phenomenon, termed sensory defensiveness, has been proposed as the potential cause of hyperactivity, hyperarousal, and negative reactions to changes in routine that are often deleterious for FXS patients. However, the lack of tools for manipulating sensory-hypersensitivity has not allowed the experimental testing required to evaluate the relevance of this hypothesis...
July 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28717238/molecular-mechanism-of-pd-1-pd-l1-blockade-via-anti-pd-l1-antibodies-atezolizumab-and-durvalumab
#5
Hyun Tae Lee, Ju Yeon Lee, Heejin Lim, Sang Hyung Lee, Yu Jeong Moon, Hyo Jeong Pyo, Seong Eon Ryu, Woori Shin, Yong-Seok Heo
In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715754/target-identification-lead-optimization-and-antitumor-evaluation-of-some-new-1-2-4-triazines-as-c-met-kinase-inhibitors
#6
Marwa H El-Wakil, Hayam M Ashour, Manal N Saudi, Ahmed M Hassan, Ibrahim M Labouta
In silico target fishing approach using PharmMapper server identified c-Met kinase as the selective target for our previously synthesized compound NCI 748494/1. This approach was validated by in vitro kinase assay which showed that NCI 748494/1 possessed promising inhibitory activity against c-Met kinase (IC50=31.70μM). Assessment of ADMET profiling, drug-likeness, drug score as well as docking simulation for the binding pose of that compound in the active site of c-Met kinase domain revealed that NCI 748494/1 could be considered as a promising drug lead...
June 27, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28714852/the-small-molecule-mimetic-agonist-trimebutine-of-adhesion-molecule-l1-contributes-to-functional-recovery-after-spinal-cord-injury-in-mice
#7
Junping Xu, Chengliang Hu, Qiong Jiang, Hongchao Pan, Huifan Shen, Melitta Schachner
Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity, and thus constitutes a viable target to promote regeneration after SCI. Since delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans, we have identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration, and neurite outgrowth in an L1-dependent manner...
July 14, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28714577/direct-laser-interference-patterning-of-cocr-alloy-surfaces-to-control-endothelial-cell-and-platelet-response-for-cardiovascular-applications
#8
Romain Schieber, Federico Lasserre, Michael Hans, Marc Fernández-Yagüe, Maribel Díaz-Ricart, Ginés Escolar, Maria-Pau Ginebra, Frank Mücklich, Marta Pegueroles
The main drawbacks of cardiovascular bare-metal stents (BMS) are in-stent restenosis and stent thrombosis as a result of an incomplete endothelialization after stent implantation. Nano- and microscale modification of implant surfaces is a strategy to recover the functionality of the artery by stimulating and guiding molecular and biological processes at the implant/tissue interface. In this study, cobalt-chromium (CoCr) alloy surfaces are modified via direct laser interference patterning (DLIP) in order to create linear patterning onto CoCr surfaces with different periodicities (≈3, 10, 20, and 32 µm) and depths (≈20 and 800 nm)...
July 17, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28710451/selection-of-complementary-foods-based-on-optimal-nutritional-values
#9
Partho Sen, Adil Mardinogulu, Jens Nielsen
Human milk is beneficial for growth and development of infants. Several factors result in mothers ceasing breastfeeding which leads to introduction of breast-milk substitutes (BMS). In some communities traditional foods are given as BMS, in others they are given as complementary foods during weaning. Improper food selection at this stage is associated with a high prevalence of malnutrition in children under 5 years. Here we listed the traditional foods from four continents and compared them with human milk based on their dietary contents...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709456/analyses-of-distribution-and-dosimetry-of-brain-metastases-in-small-cell-lung-cancer-with-relation-to-the-neural-stem-cell-regions-feasibility-of-sparing-the-hippocampus-in-prophylactic-cranial-irradiation
#10
Lei Zhao, Yan Shen, Jin-Dong Guo, Heng-Le Gu, Wen Yu, Jia-Ming Wang, Chang-Xing Lv, Jun Liu, Xu-Wei Cai, Xiao-Long Fu
BACKGROUND: This work aims to assess the feasibility of selectively sparing the hippocampus during prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC). METHODS: SCLC patients with brain metastases (BMs) diagnosed with MRI were enrolled. Lesions localized to the neural stem cell (NSC) compartments [subventricular zone (SVZ) or hippocampus] were analyzed. Patients were categorized by the total number of intracranial metastases, the therapy processes and the symptoms...
July 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28706958/toll-like-receptor-2-mediated-nf-kappa-b-pathway-activation-in-ocular-surface-epithelial-cells
#11
Aihua Hou, Min Qi Tin, Louis Tong
BACKGROUND: Gram-positive bacteria stimulate Toll-like receptor (TLR) 2 and then activate the pro-inflammatory nuclear factor-kappa B (NF-κB) pathway. As the human ocular surface is heavily colonised by gram-positive cocci bacteria, a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation. It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells...
2017: Eye and Vision (London, England)
https://www.readbyqxmd.com/read/28702990/the-relationship-of-amphipathic-beta-structures-in-the-beta-1-domain-of-apolipoprotein-b-to-the-properties-of-the-secreted-lipoprotein-particles-in-mca-rh7777-cells
#12
Medha Manchekar, Richa Kapil, Zhihuan Sun, Jere P Segrest, Nassrin Dashti
Our previous studies demonstrated that the first 1000 amino acid residues (the βα1 domain) of human apolipoprotein (apo) B-100, referred to as apoB:1000, are required for the initiation of lipoprotein assembly and the formation of a monodisperse stable phospholipid (PL)-rich particle. The objectives of this study were to: a) assess the effects on the properties of apoB truncates undergoing sequential inclusion of the amphipathic β strands in the N-terminal 700 residues of the β1 domain of apoB-100, and b) identify the subdomain in the β1 domain that is required for the formation of a microsomal triglyceride transfer protein (MTP)-dependent triacylglycerol (TAG)-rich apoB-containing particle...
July 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28697337/basement-membrane-manipulation-in-drosophila-wing-discs-affects-dpp-retention-but-not-growth-mechanoregulation
#13
Mengqi Ma, Xueya Cao, Jianli Dai, José C Pastor-Pareja
Basement membranes (BMs) are extracellular matrix polymers basally underlying epithelia, where they regulate cell signaling and tissue mechanics. Constriction by the BM shapes Drosophila wing discs, a well-characterized model of tissue growth. Recently, the hypothesis that mechanical factors govern wing growth has received much attention, but it has not been definitively tested. In this study, we manipulated BM composition to cause dramatic changes in tissue tension. We found that increased tissue compression when perlecan was knocked down did not affect adult wing size...
July 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28696151/paravertebral-brachial-plexus-blockade-in-cats-a-cadaver-study
#14
Marina C Evangelista, Beatriz P Monteiro, Graeme M Doodnaught, Pascale Benoist, Paulo V Steagall
Objectives The aims of this study were to describe the paravertebral brachial plexus (PBP) blockade in cats, and compare the spread of bupivacaine-methylene blue solution (BMS) using two volumes of injection into the PBP. Methods Six cadavers (4.4 ± 1.8 kg) randomly received 0.15 ml/kg (LOW) or 0.2 ml/kg (HIGH) per injection of BMS into the PBP. The first injection was made ventral to the transverse process of the sixth cervical vertebra (nerves C6 and C7) at the emergence of nerve roots. A second injection was performed at the edge of the cranial border of the scapula and directed ventrally towards the first rib (C8 and T1)...
July 1, 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28693276/examination-of-the-predictive-factors-of-the-response-to-whole-brain-radiotherapy-for-brain-metastases-from-lung-cancer-using-mri
#15
Shuri Aoki, Tomonori Kanda, Noriyuki Matsutani, Nobuhiko Seki, Masafumi Kawamura, Shigeru Furui, Hideomi Yamashita
Previous studies have been conducted on the prognostic factors for overall survival in patients with brain metastases (BMs) following whole brain radiotherapy (WBRT). However, there have been a small number of studies regarding the prognostic factors for the response of tumor to WBRT. The aim of the present study was to identify the predictive factors for the response to WBRT from the point of view of reduction of tumor using magnetic resonance imaging. A retrospective analysis of 62 patients with BMs from primary lung cancer treated with WBRT was undertaken...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691458/a-%C3%A2-burning%C3%A2-therapy-for-burning-mouth-syndrome-preliminary-results-with-the-administration-of-topical-capsaicin
#16
L Azzi, F Croveri, L Pasina, M Porrini, R Vinci, M Manfredini, L Tettamanti, A Tagliabue, J Silvestre-Rangil, F Spadari
Burning mouth syndrome is defined as an intraoral burning sensation for which no medical or dental cause can be found. Recently, researchers have demonstrated an altered trophism of the small nerve fibres and alterations in the numbers of TRPV-1 vanilloid receptors. Capsaicin is a molecule that is contained in hot peppers and is specifically detected by TRPV-1 vanilloid receptors that are distributed in the oral mucosae. We aimed at verifying if topical capsaicin could prove to be an effective treatment of Burning Mouth Syndrome...
April 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28691457/human-%C3%AE-2-defensin-in-oral-lichen-planus-expresses-the-degree-of-inflammation
#17
L Azzi, P Moretto, R Vinci, F Croveri, A Boggio, J Silvestre-Rangil, L Tettamanti, A Tagliabue, A Passi
Syndrome (BMS). Seventeen OLP patients, with a positive histopathologic diagnosis of the disease, were recruited into this study in order to measure the relative quantity of HBD-2 in their saliva and crevicular fluid. The values were compared with those collected from a group of 9 patients affected by the Burning Mouth Syndrome (BMS) and with a control group (CTRL) of 9 patients. There was no statistically significant difference between the groups (p=0.523; p=0.897). However, patients affected by OLP showed a dycotomic distribution of values: while 10 of them showed similar values to those found out in the other two groups, 7 patients expressed high levels of HBD-2 and 3500 pg/ml was the threshold to distinguish the subgroups...
April 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28691192/bilirubin-coating-attenuates-the-inflammatory-response-to-everolimus-coated-stents
#18
In-Ho Bae, Dae Sung Park, So-Youn Lee, Eun-Jae Jang, Jae-Won Shim, Kyung-Seob Lim, Jun-Kyu Park, Ju Han Kim, Doo Sun Sim, Myung Ho Jeong
The aim of this study was to evaluate the effects of bilirubin- and/or everolimus (EVL)-coated stents to prevent arterial neointimal hyperplasia and inflammation in vitro and in vivo. The stents were prepared by spray coating bare metal stents (BMS) with bilirubin and/or EVL. Study groups were divided into (1) BMS, (2) bilirubin-coated stents (BES), (3) commercialized stents (Synergy™; EES), and (4) bilirubin/EVL-coated stents (B-EES). The coating thickness and drug release rates were comparable to previous reports (i...
July 10, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28690193/synergistic-inhibition-of-a%C3%AE-production-by-combinations-of-%C3%AE-secretase-modulators
#19
Alan S Robertson, Lawrence G Iben, Cong Wei, Jere E Meredith, Dieter M Drexler, Martyn Banks, Gregory D Vite, Richard E Olson, Lorin A Thompson, Charles F Albright, Michael K Ahlijanian, Jeremy H Toyn
Alzheimer's disease is associated with the accumulation of amyloid-β (Aβ) in the brain. In particular, the 42-amino acid form, Aβ1-42, is thought to play a key role in the disease. It is therefore of interest that diverse compounds, known as γ-secretase modulators (GSM), can selectively decrease Aβ1-42 production without inhibiting the production of other forms of Aβ. Here we describe the novel discovery of synergistic inhibition of Aβ by certain combinations of GSMs. Cell cultures were treated with pairwise combinations of GSMs to determine how Aβ peptide production was affected...
July 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28687024/brain-metastases-from-colorectal-cancer-characteristics-and-management
#20
REVIEW
Diane Mege, Arnaud Sans, Mehdi Ouaissi, Antonio Iannelli, Igor Sielezneff
BACKGROUND: Brain metastases (BMs) are the most common intracranial neoplasms in adults, but they rarely arise from colorectal cancer (CRC). The objective of this study was to report an overview of the characteristics and current management of CRC BMs. METHODS: A systematic review on CRC BMs was performed using Medline database from 1983 to 2015. The search was limited to studies published in English. Review articles, not relevant case report or studies or studies relating to animal and in vitro experiments were excluded...
July 7, 2017: ANZ Journal of Surgery
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