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https://www.readbyqxmd.com/read/27914088/murine-mycobacterium-marinum-infection-as-a-model-for-tuberculosis
#1
Julia Lienard, Fredric Carlsson
Mycobacteria are a major human health problem globally. Regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (Manjelievskaia J et al, Trans R Soc Trop Med Hyg 110: 110, 2016; Pereira et al., Lancet Infect Dis 12:300-306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-prevention and available treatments. Thus, increased basic understanding of mycobacterial-and particularly Mycobacterium tuberculosis-virulence strategies and pathogenesis is of great importance...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913998/immunotherapy-for-breast-cancer-past-present-and-future
#2
Alison Spellman, Shou-Ching Tang
Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913856/direct-oral-anticoagulants-an-overview-for-the-interventional-radiologist
#3
Pradesh Kumar, Rajeev Ravi, Gaurav Sundar, Caroline Shiach
The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing...
December 2, 2016: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/27913581/a-proteomic-approach-to-analyse-the-aspirin-mediated-lysine-acetylome
#4
Michael H Tatham, Christian Cole, Paul Scullion, Ross Wilkie, Nicholas J Westwood, Lesley A Stark, Ronald T Hay
Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells...
December 2, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#5
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913502/mrd-in-aml-does-it-already-guide-therapy-decision-making
#6
Gert Ossenkoppele, Gerrit Jan Schuurhuis
Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [MRD]) far below the level of 5% blast cells is changing the landscape of risk classification...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913448/targeting-inflammation-in-cancer-prevention-and-therapy
#7
REVIEW
Jelena Todoric, Laura Antonucci, Michael Karin
Inflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression...
December 2016: Cancer Prevention Research
https://www.readbyqxmd.com/read/27913229/a-single-arm-phase-iii-study-exploring-the-efficacy-and-safety-of-lng-ius-8-a-low-dose-levonorgestrel-intrauterine-contraceptive-system-total-content-13-5-mg-in-an-asia-pacific-population
#8
Guangsheng Fan, Sukho Kang, Mulan Ren, Edith Weisberg, Eeva Lukkari-Lax, Katrin Roth, SoYoung Shin
OBJECTIVE: To evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approx. 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. STUDY DESIGN: An open-label, single-arm Phase III study conducted at 25 centers in China, Australia, and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days)...
November 29, 2016: Contraception
https://www.readbyqxmd.com/read/27913204/the-selective-bcl-2-inhibitor-venetoclax-a-bh3-mimetic-does-not-dysregulate-intracellular-ca-2-signaling
#9
Tamara Vervloessem, Hristina Ivanova, Tomas Luyten, Jan B Parys, Geert Bultynck
Anti-apoptotic B cell-lymphoma-2 (Bcl-2) proteins are emerging as therapeutic targets in a variety of cancers for precision medicines, like the BH3-mimetic drug venetoclax (ABT-199), which antagonizes the hydrophobic cleft of Bcl-2. However, the impact of venetoclax on intracellular Ca(2+) homeostasis and dynamics in cell systems has not been characterized in detail. Here, we show that venetoclax did not affect Ca(2+)-transport systems from the endoplasmic reticulum (ER) in permeabilized cell systems. Venetoclax (1μM) did neither trigger Ca(2+) release by itself nor affect agonist-induced Ca(2+) release in a variety of intact cell models...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27912902/evolution-of-the-clinical-profile-of-patients-with-acute-heart-failure-treated-in-spanish-emergency-departments
#10
R Escoda, Ò Miró, F J Martín-Sánchez, J Jacob, P Herrero, V Gil, J M Garrido, M J Pérez-Durá, M Fuentes, P Llorens
OBJECTIVE: To analyse the changes in epidemiology, outpatient and emergency department clinical care, and outcomes of patients treated for acute heart failure (AHF) in Spanish hospital emergency departments (HEDs) between 2007 and 2014. METHOD: A multicentre cohort study was conducted that consecutively included patients with AHF diagnosed in 9HEDs during 4 periods (2007, 2009, 2011 and 2014). The study analysed the changes observed in 20 variables corresponding to baseline data, outpatient care and emergency care data and outcome data...
November 29, 2016: Revista Clínica Española
https://www.readbyqxmd.com/read/27912871/short-term-open-label-chamomile-matricaria-chamomilla-l-therapy-of-moderate-to-severe-generalized-anxiety-disorder
#11
John R Keefe, Jun J Mao, Irene Soeller, Qing S Li, Jay D Amsterdam
BACKGROUND: Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD. HYPOTHESIS: We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912845/molecular-mechanisms-and-clinical-implications-of-bacterial-persistence
#12
Joran Elie Michiels, Bram Van den Bergh, Natalie Verstraeten, Jan Michiels
Any bacterial population harbors a small number of phenotypic variants that survive exposure to high concentrations of antibiotic. Importantly, these so-called 'persister cells' compromise successful antibiotic therapy of bacterial infections and are thought to contribute to the development of antibiotic resistance. Intriguingly, drug-tolerant persisters have also been identified as a factor underlying failure of chemotherapy in tumor cell populations. Recent studies have begun to unravel the complex molecular mechanisms underlying persister formation and revolve around stress responses and toxin-antitoxin modules...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#13
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912758/emerging-polymorphisms-in-falciparum-kelch-13-gene-in-northeastern-region-of-india
#14
Neelima Mishra, Ram Suresh Bharti, Prashant Mallick, Om Prakash Singh, Bina Srivastava, Roma Rana, Sobhan Phookan, Hardev Prasad Gupta, Pascal Ringwald, Neena Valecha
BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar...
December 3, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27912090/advances-in-zika-virus-research-stem-cell-models-challenges-and-opportunities
#15
REVIEW
Guo-Li Ming, Hengli Tang, Hongjun Song
The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection as well as platforms for drug testing...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27911896/different-mutations-in-a-p-type-atpase-transporter-in-leishmania-parasites-are-associated-with-cross-resistance-to-two-leading-drugs-by-distinct-mechanisms
#16
Christopher Fernandez-Prada, Isabel M Vincent, Marie-Christine Brotherton, Mathew Roberts, Gaétan Roy, Luis Rivas, Philippe Leprohon, Terry K Smith, Marc Ouellette
Leishmania infantum is an etiological agent of the life-threatening visceral form of leishmaniasis. Liposomal amphotericin B (AmB) followed by a short administration of miltefosine (MF) is a drug combination effective for treating visceral leishmaniasis in endemic regions of India. Resistance to MF can be due to point mutations in the miltefosine transporter (MT). Here we show that mutations in MT are also observed in Leishmania AmB-resistant mutants. The MF-induced MT mutations, but not the AmB induced mutations in MT, alter the translocation/uptake of MF...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27911847/zika-virus-cell-tropism-in-the-developing-human-brain-and-inhibition-by-azithromycin
#17
Hanna Retallack, Elizabeth Di Lullo, Carolina Arias, Kristeene A Knopp, Matthew T Laurie, Carmen Sandoval-Espinosa, Walter R Mancia Leon, Robert Krencik, Erik M Ullian, Julien Spatazza, Alex A Pollen, Caleigh Mandel-Brehm, Tomasz J Nowakowski, Arnold R Kriegstein, Joseph L DeRisi
The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#18
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911751/the-lateral-habenula-circuitry-reward-processing-and-cognitive-control
#19
Phillip M Baker, Thomas Jhou, Bo Li, Masayuki Matsumoto, Sheri J Y Mizumori, Marcus Stephenson-Jones, Aleksandra Vicentic
There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911112/treatment-of-alpha-and-beta-herpesvirus-infections-in-solid-organ-transplant-recipients
#20
C L Abad, R R Razonable
Human herpesviruses frequently cause infections in solid organ transplant (SOT) recipients. Areas covered: We provide an overview of the clinical impact of alpha and beta herpesviruses and highlight the mechanisms of action, pharmacokinetics, clinical indications, and adverse effects of antiviral drugs for the management of herpes simplex virus, varicella zoster virus and cytomegalovirus. We comprehensively evaluated key clinical trials that led to drug approval, and served as the foundation for management guidelines...
December 2, 2016: Expert Review of Anti-infective Therapy
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