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https://www.readbyqxmd.com/read/27933426/characterization-of-the-first-fully-human-anti-tem1-scfv-in-models-of-solid-tumor-imaging-and-immunotoxin-based-therapy
#1
Xiaopeng Yuan, Mingjuan Yang, Xiang Chen, Xuhua Zhang, Shrey Sukhadia, Najia Musolino, Huijing Bao, Tingtao Chen, Chen Xu, Qirui Wang, Stephen Santoro, Daniel Ricklin, Jia Hu, Ruihe Lin, Wei Yang, Zhijun Li, Weijun Qin, Aizhi Zhao
Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here, we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope...
December 8, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27932952/evaluating-tools-for-live-imaging-of-structural-plasticity-at-the-axon-initial-segment
#2
Adna S Dumitrescu, Mark D Evans, Matthew S Grubb
The axon initial segment (AIS) is a specialized neuronal compartment involved in the maintenance of axo-dendritic polarity and in the generation of action potentials. It is also a site of significant structural plasticity-manipulations of neuronal activity in vitro and in vivo can produce changes in AIS position and/or size that are associated with alterations in intrinsic excitability. However, to date all activity-dependent AIS changes have been observed in experiments carried out on fixed samples, offering only a snapshot, population-wide view of this form of plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27932068/rovalpituzumab-tesirine-a-dll3-targeted-antibody-drug-conjugate-in-recurrent-small-cell-lung-cancer-a-first-in-human-first-in-class-open-label-phase-1-study
#3
Charles M Rudin, M Catherine Pietanza, Todd M Bauer, Neal Ready, Daniel Morgensztern, Bonnie S Glisson, Lauren A Byers, Melissa L Johnson, Howard A Burris, Francisco Robert, Tae H Han, Sheila Bheddah, Noah Theiss, Sky Watson, Deepan Mathur, Bharathi Vennapusa, Hany Zayed, Satwant Lally, Donald K Strickland, Ramaswamy Govindan, Scott J Dylla, Stanford L Peng, David R Spigel
BACKGROUND: Rovalpituzumab tesirine is a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3), a novel target identified in tumour-initiating cells and expressed in more than 80% of patients with small-cell lung cancer. We aimed to assess the safety and activity of rovalpituzumab tesirine in patients who progressed after one or more previous regimen. METHODS: We conducted a phase 1 open-label study at ten cancer centres in the USA...
December 2, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27931005/microfluidic-immunosensor-for-rapid-and-highly-sensitive-salivary-cortisol-quantification
#4
V Pinto, P Sousa, S O Catarino, M Correia-Neves, G Minas
This paper presents a novel poly(dimethylsiloxane) (PDMS) microfluidic immunosensor that integrates a complementary metal-oxide-semiconductor (CMOS) optical detection system for a rapid and highly-sensitive quantification of salivary cortisol. The simple and non-invasive method of saliva sampling provides an interesting alternative to the blood, allowing a fast sampling at short intervals, relevant for many clinical diagnostic applications. The developed approach is based on the covalent immobilization of a coating antibody (Ab), a polyclonal anti-IgG, onto a treated PDMS surface...
November 30, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27929747/localized-conformational-interrogation-of-antibody-and-antibody-drug-conjugates-by-site-specific-carboxyl-group-footprinting
#5
Lucy Yan Pan, Oscar Salas-Solano, John F Valliere-Douglass
Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains...
December 8, 2016: MAbs
https://www.readbyqxmd.com/read/27928714/phase-i-study-of-nivolumab-an-anti-pd-1-antibody-in-patients-with-malignant-solid-tumors
#6
Noboru Yamamoto, Hiroshi Nokihara, Yasuhide Yamada, Takashi Shibata, Yosuke Tamura, Yoshitaka Seki, Kazunori Honda, Yuko Tanabe, Hiroshi Wakui, Tomohide Tamura
Background This study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of single and multiple doses of nivolumab in Japanese patients with malignant solid tumors. Subjects and Methods This was an open-label, dose-escalation study in 17 patients with advanced solid tumors with a life expectancy of ≥3 months. Patients were observed for 3 weeks after a single dose of nivolumab at 1, 3, 10 or 20 mg/kg, then received the same dose of nivolumab every 2 weeks until unacceptable toxicity or disease progression occurred...
December 8, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27924557/high-throughput-analysis-of-mammalian-receptor-tyrosine-kinase-activation-in-yeast-cells
#7
Nobuo Yoshimoto, Shun'ichi Kuroda
Tyrosine phosphorylation is an essential posttranslational modification in intracellular signaling molecules. Since tyrosine phosphorylation occurs in less than 0.1 % of all phosphorylated amino acids in mammalian cells, it is difficult to detect the nascent phosphotyrosine at a high signal-to-noise ratio due to high intracellular backgrounds (i.e., unexpected crosstalks among endogenous signaling molecules). In order to address this issue, we reconstituted the mammalian signaling pathway involving an extracellular ligand and a receptor tyrosine kinase (RTK) in Saccharomyces cerevisiae, a lower eukaryote that lacks endogenous tyrosine kinases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924162/a-pretargeted-approach-for-the-multimodal-pet-nirf-imaging-of-colorectal-cancer
#8
Pierre Adumeau, Kathryn E Carnazza, Christian Brand, Sean D Carlin, Thomas Reiner, Brian J Agnew, Jason S Lewis, Brian M Zeglis
The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as (89)Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery...
2016: Theranostics
https://www.readbyqxmd.com/read/27923412/effects-of-vitrification-on-blastomere-viability-and-cytoskeletal-integrity-in-mouse-embryos
#9
Zenon Oikonomou, Katerina Chatzimeletiou, Antonia Sioga, Louisa Oikonomou, Basil C Tarlatzis, Efstratios Kolibianakis
Vitrification is widely used to cryopreserve supernumerary embryos following in vitro fertilization (IVF). The mouse model was used to investigate the effects of vitrification on blastomere viability, using viability markers, and on the cytoskeleton, by analysing spindle/chromosome configurations, using confocal scanning microscopy. Ninety cleavage and morula stage dimethyl sulphoxide (DMSO)/EG vitrified mouse embryos were either processed immediately following warming for viability assessment by labelling with the fluorescent markers carboxyfluorescein-diacetate succinimidylester (CFSE) and propidium iodide (PI) or were cultured to the blastocyst stage and immunostained with α-tubulin antibody to visualize microtubules and DAPI or PI to visualize DNA...
December 7, 2016: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/27923189/sensitive-immunoassay-based-detection-of-vibrio-parahaemolyticus-using-capture-and-labeling-particles-in-a-stationary-liquid-phase-lab-on-a-chip
#10
Byunghee Park, Suk-Jung Choi
In the present study, a method was developed for detection of Vibrio parahaemolyticus based on a stationary liquid phase lab-on-a-chip (SLP LOC). The present SLP LOC comprises a sample chamber, washing chamber, and detection chamber connected by two channels. The method utilizes two types of particles: capture particles (CPs), which are magnetic nanoparticles functionalized with antibody; and labeling particles (LPs), which are silica nanoparticles functionalized with horseradish peroxidase and antibody. Samples were added to the sample chamber with CPs and LPs, forming a CP-bacteria-LP complex, and the complex was transported to the detection chamber containing chromogenic substrate solution...
December 1, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27921221/safety-and-efficacy-of-natalizumab-in-japanese-patients-with-relapsing-remitting-multiple-sclerosis-open-label-extension-study-of-a-phase-2-trial
#11
Takahiko Saida, Jun-Ichi Kira, Shuji Kishida, Takashi Yamamura, Nobuhisa Ohtsuka, Yan Ling, Shinichi Torii, Nisha Lucas, Geoffrey Kuesters, Deb Steiner, J T Tibung
INTRODUCTION: The efficacy of natalizumab was evaluated in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) in a 24-week, phase 2 bridging study. An open-label, 2-year extension study from this trial was conducted to assess the safety and efficacy of natalizumab treatment in Japanese patients. METHODS: A total of 97 patients (43 previously on placebo; 54 previously on natalizumab) who had completed the bridging study were treated with 300 mg natalizumab every 4 weeks...
December 5, 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27919567/splicing-factor-proline-glutamine-rich-is-a-novel-autoantigen-of-dermatomyositis-and-associated-with-anti-melanoma-differentiation-associated-gene-5-antibody
#12
Yuji Hosono, Ran Nakashima, Satoshi Serada, Kosaku Murakami, Yoshitaka Imura, Hajime Yoshifuji, Koichiro Ohmura, Tetsuji Naka, Tsuneyo Mimori
OBJECTIVE: Anti-MDA5 antibody positive dermatomyositis (DM) and clinically amyopathic DM (CADM) often develop into rapidly progressive interstitial lung disease, but their pathogenesis remains unclear. We observed that sera from DM/CADM patients immunoprecipitated a common 110 kDa polypeptide. We investigated this autoantigen and its clinical significance. METHODS: Autoantibodies were screened in 333 patients with various connective tissue diseases (CTDs) and 20 healthy controls (HCs) by immunoprecipitation with [(35)S]methionine-labeled HeLa cells...
December 2, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27918735/comparative-immunoexpression-of-icam-1-tgf-%C3%AE-1-and-ki-67-in-periapical-and-residual-cysts
#13
R Martins, L Armada, T-C Dos Santos, F-R Pires
BACKGROUND: This study compared the immunohistochemical expression of ki-67, transforming growth factor beta 1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in inflammatory periapical cysts and residual cysts. MATERIAL AND METHODS: The study sample was composed by 25 periapical cysts and 25 residual cysts and immunohistochemical reactions were carried out using antibodies directed against ICAM-1, TGF-β1 and ki-67. Clinical, radiological, gross, histological and immunohistochemical data were tabulated for descriptive and comparative analysis using the SPSS software and differences were considered statistically significant when p<0...
December 6, 2016: Medicina Oral, Patología Oral y Cirugía Bucal
https://www.readbyqxmd.com/read/27916899/label-free-detection-of-human-glycoprotein-cga-using-an-extended-gated-organic-transistor-based-immunosensor
#14
Tsukuru Minamiki, Tsuyoshi Minami, Yui Sasaki, Shin-Ichi Wakida, Ryoji Kurita, Osamu Niwa, Shizuo Tokito
Herein, we report on the fabrication of an extended-gated organic field-effect transistor (OFET)-based immunosensor and its application in the detection of human chromogranin A (hCgA). The fabricated OFET device possesses an extended-gate electrode immobilized with an anti-CgA antibody. The titration results of hCgA showed that the electrical changes in the OFET characteristics corresponded to the glycoprotein recognition ability of the monoclonal antibody (anti-CgA). The observed sensitivity (detection limit: 0...
November 30, 2016: Sensors
https://www.readbyqxmd.com/read/27916103/-preparation-and-application-of-mouse-anti-aeg-1-monoclonal-antibody
#15
Man Lu, Min Long, Zhaowei Gao, Chong Liu, Huizhong Zhang
Objective To prepare the fluorescein isothiocyanate (FITC)-labeled mouse monoclonal antibody (mAb) against astrocyte elevated gene-1 (AEG-1) and evaluate its binding ability to tumor cells. Methods The mouse anti-AEG-1 mAb was purified from mouse ascites. The purity and activity of the mAb were identified by SDS-PAGE, Western blotting and immunohistochemistry (IHC). The FITC labeling efficiency was examined by flow cytometry (FCM) and the binding ability of FITC-labeled mAb to tumor cells was detected by FCM and IHC...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27914953/both-secreted-and-the-cellular-levels-of-bdnf-attenuated-due-to-tau-hyperphosphorylation-in-primary-cultures-of-cortical-neurons
#16
İrem Lütfiye Atasoy, Erdinç Dursun, Duygu Gezen Ak, Derya Metin Armağan, Melek Öztürk, Selma Yılmazer
Intracellular aggregation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a major neuropathological hallmark of taupathies such as Alzheimer's disease. Okadaic acid (OKA) is a potent inhibitor of PP2A, leading to abnormal tau phosphorylation. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is selectively downregulated in AD. In this study, we investigated the effects of OKA induced tau hyperphosphorylation on secreted and cellular levels of BDNF in primary cortical neurons that were treated with 25nM OKA...
November 30, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27914744/persistence-of-bactericidal-antibodies-following-booster-vaccination-with-4cmenb-at-12-18-or-24months-and-immunogenicity-of-a-fifth-dose-administered-at-4years-of-age-a-phase-3-extension-to-a-randomised-controlled-trial
#17
Mildred A Iro, Matthew D Snape, Merryn Voysey, Sena Jawad, Adam Finn, Paul T Heath, Gianni Bona, Susanna Esposito, Javier Diez-Domingo, Roman Prymula, Adefowope Odueyungbo, Daniela Toneatto, Peter Dull, Andrew J Pollard
BACKGROUND: 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24months and characterised the antibody response to a fifth dose administered at 4years of age. METHODS: A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four)...
November 30, 2016: Vaccine
https://www.readbyqxmd.com/read/27914083/antibody-guided-molecular-imaging-of-infective-endocarditis
#18
Kenneth L Pinkston, Peng Gao, Kavindra V Singh, Ali Azhdarinia, Barbara E Murray, Eva M Sevick-Muraca, Barrett R Harvey
In this protocol, we describe the application of using a high affinity monoclonal antibody generated against the major pilin protein component of the pilin structure of Enterococcus faecalis as a PET imaging agent for enterococcal endocarditis detection. The anti-pilin -mAb 64Cu conjugate was able to specifically label enterococcal endocarditis vegetation in vivo in a rodent endocarditis model. By targeting pili, a covalently linked surface antigen extending from the bacterial surface, we provided evidence that gram-positive pilin represent a logical surface antigen to define or target an infectious agent for molecularly guided imaging...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27912069/immunogenicity-and-safety-of-southern-hemisphere-quadrivalent-inactivated-influenza-vaccine-a-phase-iii-open-label-study-of-adults-in-brazil
#19
Cristiano A F Zerbini, Rodrigo Ribeiro Dos Santos, Maria Jose Nunes, Jyoti Soni, Ping Li, Varsha K Jain, Opokua Ofori-Anyinam
The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines...
November 29, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27911374/flow-cytometric-analysis-of-particle-bound-bet-v-1-allergen-in-pm10
#20
Katrin Süring, Sabine Bach, Conny Höflich, Wolfgang Straff
Flow cytometry is a method widely used to quantify suspended solids such as cells or bacteria in a size range from 0.5 to several tens of micrometers in diameter. In addition to a characterization of forward and sideward scatter properties, it enables the use of fluorescent labeled markers like antibodies to detect respective structures. Using indirect antibody staining, flow cytometry is employed here to quantify birch pollen allergen (precisely Bet v 1)-loaded particles of 0.5 to 10 µm in diameter in inhalable particulate matter (PM10, particle size ≤10 µm in diameter)...
November 19, 2016: Journal of Visualized Experiments: JoVE
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