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https://www.readbyqxmd.com/read/28319364/a-new-spin-on-antibody-drug-conjugates-trastuzumab-fulvestrant-colloidal-drug-aggregates-target-her2-positive-cells
#1
Ahil N Ganesh, Christopher Mclaughlin, Da Duan, Brian K Shoichet, Molly S Shoichet
While the formation of colloidal aggregates leads to artifacts in early drug discovery, their composition makes them attrac-tive as nanoparticle formulations for targeted drug delivery as the entire nanoparticle is composed of drug. The typical tran-sient stability of colloidal aggregates has inhibited exploiting this property. To overcome this limitation, we investigated a series of proteins to stabilize colloidal aggregates of the chemotherapeutic, fulvestrant, including: bovine serum albumin, a generic human immunoglobulin G, and trastuzumab, a therapeutic anti-human epidermal growth factor receptor 2 anti-body...
March 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28315174/microglia-activation-contributes-to-quinolinic-acid-induced-neuronal-excitotoxicity-through-tnf-%C3%AE
#2
Wei Feng, Yan Wang, Zi-Qi Liu, Xuan Zhang, Rong Han, You-Zhu Miao, Zheng-Hong Qin
It has been reported that activation of NF-κB is involved in excitotoxicity; however, it is not fully understood how NF-κB contributes to excitotoxicity. The aim of this study is to investigate if NF-κB contributes to quinolinic acid (QA)-mediated excitotoxicity through activation of microglia. In the cultured primary cortical neurons and microglia BV-2 cells, the effects of QA on cell survival, NF-κB expression and cytokines production were investigated. The effects of BV-2-conditioned medium (BCM) on primary cortical neurons were examined...
March 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28300861/primary-cribriform-carcinoma-of-the-eyelid-with-neuroendocrine-features-a-case-report
#3
Joshua D Fox, Sander R Dubovy, Sara T Wester, Keyvan Nouri
A variety of tumors may involve the eyelid, most of which are primary, but rarely can be metastatic. Previously reported eyelid primary carcinomas with neuroendocrine features include Merkel cell carcinoma, apocrine and eccrine gland carcinoma, sebaceous gland carcinoma, and one report of primary "well-differentiated neuroendocrine tumor." Herein we report the first case of primary cribriform carcinoma of the eyelid with neuroendocrine features. The patient is a 75-year-old black man who presented to the clinic with a 5-year history of a slowly growing, non-painful, non-exudative lesion of his left lower eyelid...
February 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28287004/denosumab-reduces-early-migration-in-total-knee-replacement
#4
Håkan Ledin, Lars Good, Per Aspenberg
Background and purpose - Aseptic loosening is a main cause of late revision in total knee replacement (TKR). Migration of implants as measured by radiostereometric analysis (RSA) can predict future loosening. This migration is associated with bone resorption. Denosumab is a human monoclonal antibody that binds to receptors on osteoclast precursors and osteoclasts. This prevents osteoclast formation, resulting in less bone resorption in cortical and trabecular bone. We investigated whether denosumab can reduce migration of TKR, as measured with RSA...
March 13, 2017: Acta Orthopaedica
https://www.readbyqxmd.com/read/28285402/a-semi-empirical-glycosylation-model-of-a-camelid-monoclonal-antibody-under-hypothermia-cell-culture-conditions
#5
Hengameh Aghamohseni, Maureen Spearman, Kaveh Ohadi, Katrin Braasch, Murray Moo-Young, Michael Butler, Hector M Budman
The impact of cell culture environment on the glycan distribution of a monoclonal antibody (mAb) has been investigated through a combination of experiments and modeling. A newly developed CHO DUXB cell line was cultivated at two levels of initial Glutamine (Gln) concentrations (0, 4 mM) and incubation temperatures of (33 and 37 °C) in batch operation mode. Hypothermia was applied either through the entire culture duration or only during the post-exponential phase. Beyond reducing cell growth and increasing productivity, hypothermia significantly altered the galactosylation index profiles as compared to control conditions...
March 11, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28278327/chorioretinal-lesions-presumed-secondary-to-zika-virus-infection-in-an-immunocompromised-adult
#6
Christopher R Henry, Luma Al-Attar, Alexis M Cruz-Chacón, Janet L Davis
Importance: Zika virus has spread rapidly throughout the Americas since 2015. The public health implications of Zika virus infection lend special importance to identifying the virus in unsuspected hosts. Objective: To describe relevant imaging studies and clinical features of chorioretinal lesions that are presumably associated with Zika virus and that share analogous features with chorioretinal lesions reported in cases of Dengue fever and West Nile virus. Design, Setting, and Participants: This is a case report from an academic referral center in Miami, Florida, of a woman in her 60s from Guaynabo, Puerto Rico, who presented with reduced visual acuity and bilateral diffuse, subretinal, confluent, placoid, and multifocal chorioretinal lesions...
March 9, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28276249/functional-modification-of-electrospun-poly-%C3%AE%C2%B5-caprolactone-vascular-grafts-with-the-fusion-protein-vegf-hgfi-enhanced-vascular-regeneration
#7
Kai Wang, Qiuying Zhang, Liqiang Zhao, Yiwa Pan, Ting Wang, Dengke Zhi, Shaoyang Ma, Peixin Zhang, Tiechan Zhao, Siming Zhang, Wen Li, Meifeng Zhu, Yan Zhu, Jun Zhang, Mingqiang Qiao, Deling Kong
Synthetic artificial vascular grafts have exhibited low patency rate and severe neointimal hyperplasia in replacing small-caliber arteries (<6 mm) because of their failure to generate a functional endothelium. In this study, small-caliber (2.0 mm) electrospun poly(ε-caprolactone) (PCL) vascular grafts were modified with a fusion protein VEGF-HGFI which consists of the class I hydrophobin (HGFI) and vascular endothelial growth factor (VEGF), via hydrophobic interactions. Immunofluorescence staining with the anti-VEGF antibody showed that VEGF-HGFI formed a protein layer on the surface of fibers in the grafts...
March 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28274481/no-detection-of-varicella-zoster-virus-in-temporal-arteries-of-patients-with-giant-cell-arteritis
#8
Francesco Muratore, Stefania Croci, Ione Tamagnini, Alessandro Zerbini, Salvatore Bellafiore, Lucia Belloni, Luigi Boiardi, Alessandra Bisagni, Nicolò Pipitone, Maria Parmeggiani, Alberto Cavazza, Carlo Salvarani
OBJECTIVE: Data on the presence of varicella-zoster virus (VZV) in temporal arteries of patients with giant cell arteritis (GCA) are controversial. We analyzed VZV infection in temporal arteries from Italian patients with temporal artery biopsy (TAB)-positive GCA, TAB-negative GCA, and controls. METHODS: A total of 79 formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 at a single institution from 34 TAB-positive GCA patients, 15 TAB-negative GCA patients, and 30 controls were retrieved...
February 10, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28272216/nonorgan-specific-autoantibodies-in-hiv-infected-patients-in-the-haart-era
#9
Laura Iordache, Djaouida Bengoufa, Olivier Taulera, Agathe Rami, Caroline Lascoux-Combe, Nesrine Day, Maguy Parrinello, Pierre-Olivier Sellier, Jean-Michel Molina, Alfred Mahr
Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status.Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-β2glycoprotein1 (anti-β2GP1), and antineutrophil cytoplasmic antibodies (ANCAs)...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28270081/tocilizumab-labeling-with-99mtechnetium-via-hynic-as-a-molecular-diagnostic-agent-for-multiple-myeloma
#10
Ximena Camacho, Camila Longo Machado, Maria Fernanda García, Marcelo Fernández, Natalia Oddone, Juan Benech, Juan Pablo Gambini, Hugo Cerecetto, Roger Chammas, Pablo Cabral, Eloisa Riva
BACKGROUND: Multiple myeloma (MM) incidence and mortality is increasing worldwide. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. OBJECTIVE: To radiolabel Tocilizumab with 99mTechnetium as a potential imaging agents for MM. METHODS: IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S)...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28262555/membrane-proximal-epitope-facilitates-efficient-t-cell-synapse-formation-by-anti-fcrh5-cd3-and-is-a-requirement-for-myeloma-cell-killing
#11
Ji Li, Nicola J Stagg, Jennifer Johnston, Michael J Harris, Sam A Menzies, Danielle DiCara, Vanessa Clark, Maria Hristopoulos, Ryan Cook, Dionysos Slaga, Rin Nakamura, Luke McCarty, Siddharth Sukumaran, Elizabeth Luis, Zhengmao Ye, Thomas D Wu, Teiko Sumiyoshi, Dimitry Danilenko, Genee Y Lee, Klara Totpal, Diego Ellerman, Isidro Hötzel, John R James, Teemu T Junttila
The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys...
February 20, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28261207/investigating-substitutions-in-antibody-antigen-complexes-using-molecular-dynamics-a-case-study-with-broad-spectrum-influenza-a-antibodies
#12
William D Lees, Lenka Stejskal, David S Moss, Adrian J Shepherd
In studying the binding of host antibodies to the surface antigens of pathogens, the structural and functional characterization of antibody-antigen complexes by X-ray crystallography and binding assay is important. However, the characterization requires experiments that are typically time consuming and expensive: thus, many antibody-antigen complexes are under-characterized. For vaccine development and disease surveillance, it is often vital to assess the impact of amino acid substitutions on antibody binding...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28259300/immunotherapy-for-the-treatment-of-multiple-myeloma
#13
REVIEW
Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28249894/targeting-cd38-suppresses-induction-and-function-of-t-regulatory-cells-to-mitigate-immunosuppression-in-multiple-myeloma
#14
Xiaoyan Feng, Li Zhang, Chirag Acharya, Gang An, Kenneth Wen, Luqui Qiu, Nikhil C Munshi, Yu-Tzu Tai, Kenneth C Anderson
PURPOSE: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ Tregs and further define immune modulating effects of a therapeutic CD38 monoclonal antibody (mAb) Isatuximab (Isa)/SAR650984 in multiple myeloma (MM). EXPERIMENTAL DESIGN: We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and MM patients. PBMCs were then treated with Isa with or without Lenalidomide (Len) or Pomalidomide (Pom) to identify their impact on percentage and immunosuppressive activity of Tregs on CD4+CD25- T cells (Tcons)...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28246453/preparation-of-goat-and-rabbit-anti-camel-immunoglobulin-g-whole-molecule-labeled-with-horseradish-peroxidase
#15
Eman Hussein Abdel-Rahman, Jakeen Kamal El-Jakee, Mahmoud Essam Hatem, Nagwa Sayed Ata, Ehab Ali Fouad
AIM: As the labeled anti-camel immunoglobulins (Igs) with enzymes for enzyme-linked immunosorbent assay (ELISA) are unavailable in the Egyptian market, the present investigation was directed for developing local labeled anti-camel IgG with horseradish peroxidase (HRP) to save hard curacy. MATERIALS AND METHODS: For purification of camel IgG whole molecule, camel sera was preliminary precipitated with 50% saturated ammonium sulfate and dialyzed against 15 mM phosphate-buffered saline pH 7...
January 2017: Veterinary World
https://www.readbyqxmd.com/read/28240241/calcium-pre-conditioning-substitution-enhances-viability-and-glucose-sensitivity-of-pancreatic-beta-cells-encapsulated-using-polyelectrolyte-multilayer-coating-method
#16
Niusha Nikravesh, Sophie C Cox, Gurpreet Birdi, Richard L Williams, Liam M Grover
Type I diabetics are dependent on daily insulin injections. A therapy capable of immunoisolating pancreatic beta-cells and providing normoglycaemia is an alternative since it would avoid the late complications associated with insulin use. Here, 3D-concave agarose micro-wells were used to culture robust pancreatic MIN-6 cell spheroids within 24 hours that were shown to exhibit cell-cell contact and uniform size (201 ± 2 μm). A polyelectrolyte multilayer (PEM) approach using alginate and poly-l-lysine was employed to coat cell spheroids...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28240019/differential-expression-of-glypican-3-and-insulin%C3%A2-like-growth-factor-ii-mrnas-and-alpha-fetoprotein-and-ki-67-markers-in-hcv-related-hepatocellular-carcinomas-in-egyptian-patients
#17
Mohamed A Saber, Samah MM AbdelHafiz, Fatma E Khorshed, Tarek S Aboushousha, Hussam EM Hamdy, Mohamed I Seleem, Amira H Soliman
Background: Increasing evidence indicates that in hepatocellular carcinomas (HCCs) abnormal gene expression, for example of glypican-3 (GPC-3) and insulin-like growth factor-II (IGF-II), are associated with the occurrence and progression of HCC. The objective of this study was to evaluate the differential expression of GPC-3 and IGF-II mRNAs in HCC tissues with a background of chronic hepatitis C virus (HCV) genotype 4 cirrhosis, in relation to Ki-67 and alpha-feto protein (AFP) tissue markers. Methods: One hundred and five patients with HCCs who had undergone hepatectomy, were included, after obtaining informed consent...
January 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28236056/influence-of-membrane-receptor-lateral-diffusion-on-the-short-term-depression-of-acetylcholine-induced-current-in-helix-neurons
#18
Natalia A Vasilyeva, Galina B Murzina, Igor I Kireev, Arkady S Pivovarov
We have studied how various drugs increasing the rate of nicotinic acetylcholine receptors (nAChRs) lateral diffusion affect the depression of ACh-induced current in land snail Helix lucorum neurons responsible for defensive behavior. The acetylcholine (ACh) iontophoretic application protocol imitated the behavioral habituation protocol for the intact animal. We found that the drugs decreasing cholesterol level in cell membranes as methyl-β-cyclodextrin 1 mM and Ro 48-8071 2 µM, and polyclonal antibodies to actin-binding proteins as spectrin 5 µg/ml and merlin 2...
February 24, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28231031/different-serological-profiles-to-cooccurring-pathogenic-and-nonpathogenic-caliciviruses-in-wild-european-rabbits-oryctolagus-cuniculus-across-australia
#19
Tanya E Cox, June Liu, Remy van de Ven, Tanja Strive
Rabbit hemorrhagic disease virus (RHDV) was released in Australia as a biocontrol agent for wild European rabbits ( Oryctolagus cuniculus ) in 1995-96; however, its effects were variable across Australia with the greatest population reductions seen in lower annual rainfall areas (<400 mm). There is speculation that the reduced effectiveness observed at higher annual rainfall sites is at least partially due to the presence of a nonpathogenic calicivirus (RCV-A1). The RCV-A1 is related to RHDV and confers partial and transient protection against lethal RHDV infection in laboratory tests...
February 23, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28229991/a-novel-mutation-in-the-pyrin-domain-of-the-nod-like-receptor-family-pyrin-domain-containing-protein-3-in-muckle-wells-syndrome
#20
Jian Hu, Yun Zhu, Jian-Zhong Zhang, Rong-Guang Zhang, Hou-Min Li
BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin (IL)-1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease. CAPS is associated with gain-of-function missense mutations in NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), the gene encoding NLRP3...
2017: Chinese Medical Journal
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