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https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#1
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28917247/the-optimism-surrounding-stereotactic-body-radiation-therapy-and-immunomodulation
#2
Hannah Tharmalingam, Peter J Hoskin
In recent years, rapidly evolving radiation techniques have enabled the precise delivery of very high doses of radiation to local targets with stereotactic ablative body radiotherapy (SABR). In addition to its direct cytotoxicity, radiation and in particular SABR has powerful immunomodulatory effects resulting in immunogenic cell death and potentiation of the anti-tumour immune response. However, due to the immunosuppressive nature of non-irradiated sites of metastases, radiotherapy alone is seldom sufficient to induce the systemic response required for distant tumour rejection...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28915511/children-s-comprehension-of-object-relative-sentences-it-s-extant-language-knowledge-that-matters-not-domain-general-working-memory
#3
Yazmin Ahmad Rusli, James W Montgomery
Purpose: The aim of this study was to determine whether extant language (lexical) knowledge or domain-general working memory is the better predictor of comprehension of object relative sentences for children with typical development. We hypothesized that extant language knowledge, not domain-general working memory, is the better predictor. Method: Fifty-three children (ages 9-11 years) completed a word-level verbal working-memory task, indexing extant language (lexical) knowledge; an analog nonverbal working-memory task, representing domain-general working memory; and a hybrid sentence comprehension task incorporating elements of both agent selection and cross-modal picture-priming paradigms...
September 15, 2017: Journal of Speech, Language, and Hearing Research: JSLHR
https://www.readbyqxmd.com/read/28898717/targeting-dendritic-cells-through-gold-nanoparticles-a-review-on-the-cellular-uptake-and-subsequent-immunological-properties
#4
REVIEW
Suhana Ahmad, Anes Ateqah Zamry, Hern-Tze Tina Tan, Kah Keng Wong, JitKang Lim, Rohimah Mohamud
Gold nanoparticles (NPs) have been proposed as a highly potential tool in immunotherapies due to its advantageous properties including customizable size and shapes, surface functionality and biocompatibility. Dendritic cells (DCs), the sentinels of immune response, have been of interest to be manipulated by using gold NPs for targeted delivery of immunotherapeutic agent. Researches done especially in human DCs showed a variation of gold NPs effects on cellular uptake and internalization, DC maturation and subsequent T cells priming as well as cytotoxicity...
September 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28898188/contrast-enhanced-us-approach-to-the-diagnosis-of-focal-liver-masses
#5
David P Burrowes, Alexandra Medellin, Allison C Harris, Laurent Milot, Stephanie R Wilson
Focal liver lesions are commonly encountered and often demonstrate nonspecific findings at initial imaging. Although most incidentally discovered liver lesions are benign, their noninvasive diagnosis is necessary, especially if they are large or atypical. Imaging characterization of focal liver lesions and exclusion of malignancy are of prime importance, particularly in high-risk populations. Contrast agent-enhanced ultrasonography of liver lesions is both accurate and reproducible for evaluation of benign and malignant liver tumors...
September 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28893044/immuno-histochemical-and-quantitative-study-of-melanocytes-and-melanin-granules-in-oral-epithelial-dysplasia
#6
Swapna Honwad, S V Ravi, Mandana Donoghue, Manjiri Joshi
INTRODUCTION: Oral Epithelial dysplasia (OED) is a potentially malignant disorder that is characterized by the presence of architectural and cytological changes. One of the prime factors responsible for the development of these lesions is the usage of tobacco. A variety of factors provide protective mechanism in order to prevent the effects of chemotoxic agents including tobacco products of which, melanin pigmentation is one of the vital elements. AIM: Role of melanocytes in progression of OED has remained unclear, so the present study was done to evaluate density of melanocyte and melanin granules in different grades of epithelial dysplasia and to correlate both findings with different grades of epithelial dysplasia...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#7
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28887912/safety-profile-of-good-manufacturing-practice-manufactured-interferon-%C3%AE-primed-mesenchymal-stem-stromal-cells-for-clinical-trials
#8
Adam J Guess, Beth Daneault, Rongzhang Wang, Hillary Bradbury, Krista M D La Perle, James Fitch, Sheri L Hedrick, Elizabeth Hamelberg, Caroline Astbury, Peter White, Kathleen Overolt, Hemalatha Rangarajan, Rolla Abu-Arja, Steven M Devine, Satoru Otsuru, Massimo Dominici, Lynn O'Donnell, Edwin M Horwitz
Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule...
September 9, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28884113/in-vitro-culture-of-na%C3%A3-ve-human-bone-marrow-mesenchymal-stem-cells-a-stemness-based-approach
#9
REVIEW
Bidisha Pal, Bikul Das
Human bone marrow derived mesenchymal stem cells (BM-MSCs) resides in their niches in close proximity to hematopoietic stem cells (HSCs). These naïve MSCs have tremendous potential in regenerative therapeutics, and may also be exploited by cancer and infectious disease agents. Hence, it is important to study the physiological and pathological roles of naïve MSC. However, our knowledge of naïve MSCs is limited by lack of appropriate isolation and in vitro culture methods. Established culture methods use serum rich media, and serial passaging for retrospective isolation of MSCs...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28881739/a-phase-i-trial-of-azacitidine-and-nanoparticle-albumin-bound-paclitaxel-in-patients-with-advanced-or-metastatic-solid-tumors
#10
Adam L Cohen, Abhijit Ray, Matthew Van Brocklin, David M Burnett, Randy C Bowen, Donna L Dyess, Thomas W Butler, Theresa Dumlao, Hung T Khong
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877735/priming-astrocytes-with-tnf-enhances-their-susceptibility-to-trypanosoma-cruzi-infection-and-creates-a-self-sustaining-inflammatory-milieu
#11
Andrea Alice Silva, Rafael Rodrigues Silva, Daniel Gibaldi, Rafael Meyer Mariante, Jessica Brandão Dos Santos, Isabela Resende Pereira, Otacílio Cruz Moreira, Joseli Lannes-Vieira
BACKGROUND: In conditions of immunosuppression, the central nervous sty 5ystem (CNS) is the main target tissue for the reactivation of infection by Trypanosoma cruzi, the causative agent of Chagas disease. In experimental T. cruzi infection, interferon gamma (IFNγ)(+) microglial cells surround astrocytes harboring amastigote parasites. In vitro, IFNγ fuels astrocyte infection by T. cruzi, and IFNγ-stimulated infected astrocytes are implicated as potential sources of tumor necrosis factor (TNF)...
September 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28874022/ex-vivo-administration-of-trimetazidine-improves-post-transplant-lung-function-in-pig-model
#12
Tugba Cosgun, Ilker Iskender, Yoshito Yamada, Stephan Arni, Miriam Lipiski, Koen van Tilburg, Walter Weder, Ilhan Inci
OBJECTIVES: Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. METHODS: Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each)...
July 1, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28870635/cannabidiol-inhibits-priming-induced-reinstatement-of-methamphetamine-in-rem-sleep-deprived-rats
#13
Saeideh Karimi-Haghighi, Abbas Haghparast
Methamphetamine (METH) is a widely abused and a severely addictive psychostimulant. Relapse is the main cause of concern when treating addiction. It could manifest after a long period of abstinence. Previous studies showed that there is a strong connection between sleep impairment and relapse. Also, it has been reported that cannabidiol might be a potential treatment for drug craving and relapse. In this study, we used conditioned place preference (CPP) to investigate whether Cannabidiol (CBD), a phytocannabinoid, can prevent METH-induced reinstatement in Rapid Eye Movement Sleep Deprived (RSD) rats...
September 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28869548/polymethoxyflavones-novel-%C3%AE-secretase-bace1-inhibitors-from-citrus-peels
#14
Kumju Youn, Yoonjin Yu, Jinhyuk Lee, Woo-Sik Jeong, Chi-Tang Ho, Mira Jun
Beta-site amyloid precursor protein (APP) cleaving enzyme1 (BACE1) catalyzes the rate-limiting step of amyloid-β protein (Aβ) generation, and is considered as a prime target for Alzheimer's disease (AD). In search of a candidate for AD prevention, our efforts exploring the natural BACE1 inhibitor have led to the finding of nobiletin, tangeretin, and sinensetin-representative compounds of polymethoxyflavones (PMFs). Tangeretin exhibited the strongest BACE1 inhibition (IC50, 4.9 × 10(-5) M), followed by nobiletin and sinensetin with IC50 values of 5...
September 4, 2017: Nutrients
https://www.readbyqxmd.com/read/28838267/immunogenicity-and-efficacy-of-dna-mva-hiv-vaccines-in-rhesus-macaque-models
#15
Lynette Siv Chea, Rama Rao Amara
Despite 30 years of research on HIV, a vaccine to prevent infection and limit disease progression remains elusive. The RV144 trial showed moderate, but significant protection in humans and highlighted the contribution of antibody responses directed against HIV envelope as an important immune correlate for protection. Efforts to further build upon the progress include the use of a heterologous prime-boost regimen using DNA as the priming agent and the attenuated vaccinia virus, Modified Vaccinia Ankara (MVA), as a boosting vector for generating protective HIV-specific immunity...
September 4, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28827848/biocompatibility-evaluation-of-four-dentin-adhesives-used-as-indirect-pulp-capping-materials
#16
Olga Cortés, Antonia Alcaina, Antonia Bernabé
BACKGROUND: In many cases, the indirect pulp treatment (IPT) is an acceptable treatment for deciduous teeth with reversible pulp inflammation. Various medicaments have been used for IPT, ranging from calcium hydroxide and glass ionomers to dentin adhesives. OBJECTIVE: This in vitro trial aimed to measure cytotoxicity in a cell culture, comparing the following four adhesives: Xeno® V (XE), Excite® F DSC (EX), Adhese® OneF (AD) and Prime & Bond NT (PB). MATERIALS AND METHODS: The adhesives were prepared according to the manufacturer's instructions...
June 2017: Acta Stomatologica Croatica
https://www.readbyqxmd.com/read/28827286/anti-cancer-drug-hmba-acts-as-an-adjuvant-during-intracellular-bacterial-infections-by-inducing-type-i-ifn-through-sting
#17
Akshamal Mihiranga Gamage, Kok-Onn Lee, Yunn-Hwen Gan
The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 dependent process. However, the effect of HMBA on the immune response has not been explored. We observed that pretreatment of human peripheral blood mononuclear cells with HMBA led to a markedly increased production of IL-12 and IFN-γ, but not of TNF-α, IL-6, and IL-8 upon subsequent infection with Burkholderia pseudomallei and Salmonella enterica HMBA treatment was also associated with better intracellular bacterial control...
August 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28821767/identification-of-candidate-genes-for-devil-facial-tumour-disease-tumourigenesis
#18
Robyn L Taylor, Yiru Zhang, Jennifer P Schöning, Janine E Deakin
Devil facial tumour (DFT) disease, a transmissible cancer where the infectious agent is the tumour itself, has caused a dramatic decrease in Tasmanian devil numbers in the wild. The purpose of this study was to take a candidate gene/pathway approach to identify potentially perturbed genes or pathways in DFT. A fusion of chromosome 1 and X is posited as the initial event leading to the development of DFT, with the rearranged chromosome 1 material now stably maintained as the tumour spreads through the population...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815933/an-%C3%AE-iib-%C3%AE-3-antagonist-prevents-thrombosis-without-causing-fc%C3%AE-riia-mediated-thrombocytopenia
#19
Yu-Ju Kuo, Ying-Ru Chen, Chun-Chieh Hsu, Hui-Chin Peng, Tur-Fu Huang
BACKGROUND: Thrombocytopenia, a common side effect of Arg-Gly-Asp (RGD)-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin αIIb β3 . OBJECTIVE: To explore the correlation between αIIb β3 binding epitopes and induction of DDAb binding to conformation-altered αIIb β3 , we examined whether two purified disintegrins TMV-2 and TMV-7 with distinct binding motifs that have different effects on induction of αIIb β3 conformational change and platelet aggregation in the presence of AP2, an IgG1 inhibitory monoclonal antibody (mAb) raised against αIIb β3 ...
August 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28814364/effect-of-cured-versus-uncured-adhesive-inclusion-on-the-microtensile-bond-strength-of-sealants
#20
Austin McMurphy, Xiaoming Xu, Suzanne Fournier, Zafer C Cehreli, Kramer Sherman, Courtney Tremmel, Qingzhao Yu, Janice Townsend
PURPOSE: To determine the impact of light curing of bonding agents on the microtensile bond strength (MTBS) of sealants on extracted teeth. METHODS: Flat enamel surfaces were created on 54 extracted, sound human molars by sequential grinding. Three different sealants- Clinpro (3M ESPE), Ultraseal XT Hydro (Ultradent), and Fluorshield VLC (Dentsply)- were placed after acid etching without a bonding agent (control) or with three different bonding agents - Adper Single Bond Plus (3M ESPE), Peak Universal Bond (Ultradent), and Prime&Bond Elect (Dentsply)- each in both light-cured and uncured form...
May 15, 2017: Journal of Dentistry for Children
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