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https://www.readbyqxmd.com/read/29352771/severe-cutaneous-adverse-reactions-due-to-inappropriate-medication-use
#1
G Chaby, L Valeyrie-Allanore, T A Duong, B Lebrun-Vignes, B Milpied, B Sassolas, F Tetart, P Wolkenstein, O Chosidow, L Fardet
BACKGROUD: The proportion of severe cutaneous adverse reactions (SCARs) that could be avoided if medication use was consistent with good medical practice is unknown. OBJECTIVES: To estimate the proportion of SCARs related to inappropriate medication use. METHODS: Retrospective study of all validated SCARs collected in a French registry between 2003 and 2016. For each case, all plausible drugs suspected to induce SCARs (i.e., not just the drug regarded as "the most probable") were considered regarding three causes of preventability: (1) prescription for an inappropriate indication, (2) unintentional rechallenge despite a previous allergy to the drug, or (3) self-medication with prescription medicines...
January 20, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#2
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352660/clinical-significance-of-muc13-in-pancreatic-ductal-adenocarcinoma
#3
Sheema Khan, Nadeem Zafar, Shabia S Khan, Saini Setua, Stephen W Behrman, Zachary E Stiles, Murali M Yallapu, Peeyush Sahay, Hemendra Ghimire, Tomoko Ise, Satoshi Nagata, Lei Wang, Jim Y Wan, Prabhakar Pradhan, Meena Jaggi, Subhash C Chauhan
BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses...
January 15, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29352646/synthesis-and-biological-evaluation-of-anti-cancer-agents-that-selectively-inhibit-her2-over-expressed-breast-cancer-cell-growth-via-down-regulation-of-her2-protein
#4
Anran Zhao, Qiaoyun Zheng, Cody M Orahoske, Nethrie D Idippily, Morgan M Ashcraft, Aicha Quamine, Bin Su
Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein...
January 12, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29352645/diversity-oriented-synthesis-of-chromene-xanthene-hybrids-as-anti-breast-cancer-agents
#5
M Srinivas Lavanya Kumar, Jyotsana Singh, Sudipta Kumar Manna, Saroj Maji, Rituraj Konwar, Gautam Panda
A diverse library of chromene-xanthene hybrids were synthesized through intramolecular Friedel-Crafts reaction of the arenoxy carbinols. Examples include first incorporation of amino acid tyrosine into xanthene skeletons with polar functionalities. A careful structural evaluation revealed that tyrosine crafted chromene-xanthene hybrids exhibited good activities against breast cancer cell lines MCF-7, MDA-MB-231. The lead compound 16 displays significant cell cycle arrest at G1 phase and induces apoptosis in MDA-MB-231 cells...
January 6, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29352490/oral-lichenoid-reaction-showing-multiple-ulcers-associated-with-anti-programmed-death-cell-receptor-1-treatment-a-report-of-two-cases-and-published-work-review
#6
Koya Obara, Mamiko Masuzawa, Yasuyuki Amoh
Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment opinion for advanced melanoma and non-small-cell lung cancer, as well as other cancerous entities. Immune checkpoint inhibitors such as anti-PD-1 antibody result in a unique side-effect profile, commonly described as immune-related adverse events (irAE). These irAE affect the skin, gastrointestinal tract, liver, endocrine system and other organ systems. We report two cases of oral lichenoid reaction showing multiple ulcers associated with nivolumab treatment...
January 20, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#7
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#8
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352425/safety-and-efficacy-of-nanocurcumin-as-add-on-therapy-to-riluzole-in-patients-with-amyotrophic-lateral-sclerosis-a-pilot-randomized-clinical-trial
#9
Mona Ahmadi, Elmira Agah, Shahriar Nafissi, Mahmoud Reza Jaafari, Mohammad Hossein Harirchian, Payam Sarraf, Sara Faghihi-Kashani, Seyed Jalal Hosseini, Abdolreza Ghoreishi, Vajiheh Aghamollaii, Mostafa Hosseini, Abbas Tafakhori
The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list...
January 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29352328/attenuation-of-serotonin-induced-itch-by-sumatriptan-possible-involvement-of-endogenous-opioids
#10
Nazgol-Sadat Haddadi, Arash Foroutan, Saeed Shakiba, Khashayar Afshari, Sattar Ostadhadi, Maryam Daneshpazhooh, Ahmad-Reza Dehpour
Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter in itch and impaired serotonin signaling has been linked to a variety of itch conditions. Intradermal injection of 5-HT induces scratching behavior in mice through stimulation of 5-HT receptors. Previous studies have demonstrated that selective 5-HT1B/1D receptors agonists, including sumatriptan, inhibits neurotransmission. We have also reported that sumatriptan suppresses chloroquine-induced itch. Therefore, we investigated if sumatriptan has inhibitory effects on serotonin-induced itch in mice...
January 19, 2018: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29352327/limk-cofilin-pathway-and-slingshot-are-implicated-in-human-colorectal-cancer-progression-and-chemoresistance
#11
Helen Aggelou, Panagiota Chadla, Sofia Nikou, Sofia Karteri, Ioannis Maroulis, Haralabos P Kalofonos, Helen Papadaki, Vasiliki Bravou
Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB...
January 19, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29352306/prognostic-and-predictive-role-of-egfr-pathway-alterations-in-biliary-cancer-patients-treated-with-chemotherapy-and-anti-egfr
#12
Caterina Peraldo-Neia, Giuliana Cavalloni, Elisabetta Fenocchio, Celeste Cagnazzo, Loretta Gammaitoni, Stefano Cereda, Guglielmo Nasti, Maria Antonietta Satolli, Giuseppe Aprile, Michele Reni, Antonio Avallone, Rosella Spadi, Tiziana Venesio, Vittoria Martin, Claudio Doglioni, Milo Frattini, Massimo Aglietta, Francesco Leone
The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH)...
2018: PloS One
https://www.readbyqxmd.com/read/29352300/5-aminosalicylic-acid-improves-lipid-profile-in-mice-fed-a-high-fat-cholesterol-diet-through-its-dual-effects-on-intestinal-ppar%C3%AE-and-ppar%C3%AE
#13
Zheng Wang, Debby Koonen, Marten Hofker, Zhijun Bao
Obesity is associated with a series of metabolic complications, including dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent years, intestinal inflammation has been suggested to contribute to obesity related metabolic syndrome and targeting gut inflammation with 5-ASA improves diet induced IR, however, its role in dyslipidemia is unknown and has never been explored. In the present study, we reported for the first time that administration of 5-ASA for 12 weeks significantly improved lipid profile by repressing plasma triglycerides and free cholesterol levels in mice fed high-fat cholesterol diet (HFC)...
2018: PloS One
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#14
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352287/ifn%C3%AE-inhibits-g-csf-induced-neutrophil-expansion-and-invasion-of-the-cns-to-prevent-viral-encephalitis
#15
Chandran Ramakrishna, Edouard M Cantin
Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#16
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352270/non-canonical-wnt-induces-chondrocyte-de-differentiation-through-frizzled-6-and-dvl-2-b-raf-camkii%C3%AE-syndecan-4-axis
#17
Zhe Xie, Mostafa Khair, Irfan Shaukat, Patrick Netter, Didier Mainard, Lydia Barré, Mohamed Ouzzine
Dysregulation of Wnt signaling has been implicated in developmental defects and in the pathogenesis of many diseases such as osteoarthritis; however, the underlying mechanisms are poorly understood. Here, we report that non-canonical Wnt signaling induced loss of chondrocyte phenotype through activation of Fz-6/DVL-2/SYND4/CaMKIIα/B-raf/ERK1/2 cascade. We show that in response to Wnt-3a, Frizzled 6 (Fz-6) triggers the docking of CaMKIIα to syndecan 4 (SYND4) and that of B-raf to DVL-2, leading to the phosphorylation of B-raf by CaMKIIα and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling, which leads to chondrocyte de-differentiation...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352248/combined-use-of-epcam-and-fr%C3%AE-enables-the-high-efficiency-capture-of-circulating-tumor-cells-in-non-small-cell-lung-cancer
#18
Luojun Chen, Min Peng, Na Li, Qibin Song, Yi Yao, Bin Xu, Huali Liu, Peng Ruan
Circulating tumor cells (CTCs) provide a new approach for auxiliary diagnosis, therapeutic effect evaluation, and prognosis prediction for cancer patients. The epithelial cell adhesion molecule (EpCAM)-based separation method (CellSearch) showed good clinical use in multiple types of cancer. Nevertheless, some non-small cell lung cancer (NSCLC) tumor cells have a lower expression of EpCAM and are less frequently detected by CellSearch. Here, we present a highly sensitive immunomagnetic separation method to capture CTCs based on two cell surface markers for NSCLC, EpCAM and Folate receptor alpha (FRα)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352243/nucleolin-and-erbb2-inhibition-reduces-tumorigenicity-of-erbb2-positive-breast-cancer
#19
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352206/omega-3-carboxylic-acids-provide-efficacious-anti-inflammatory-activity-in-models-of-crystal-mediated-inflammation
#20
Cory Iverson, Andrew Bacong, Sha Liu, Scott Baumgartner, Torbjörn Lundström, Jan Oscarsson, Jeffrey N Miner
This study assesses the efficacy and exposure-response relationship of omega-3-carboxylic acids (OM-3 CA) in models of crystal-based inflammation. Human THP-1 macrophages and primary peripheral blood mononuclear cells exposed to multiple inflammatory crystal types were used to determine the anti-inflammatory potential of omega-3 (OM-3) fatty acids in vitro. Anti-inflammatory effects of OM-3 CA in vivo were tested in rat monosodium urate (MSU) crystal air pouch and rat knee intra-articular MSU injection models...
January 19, 2018: Scientific Reports
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