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https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#1
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28432000/determination-of-thiol-to-protein-ratio-and-drug-to-antibody-ratio-by-in-line-size-exclusion-chromatography-with-post-column-reaction
#2
Kenichiro Furuki, Toshimasa Toyo'oka
An in-line size-exclusion (SE) ultra-high-performance liquid chromatography (UHPLC)- 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) method to quantify thiols in monoclonal antibodies (mAb) when manufacturing antibody-drug conjugates (ADCs) was developed. The mAbs are separated on an SE-UHPLC column and monitored with a UV detector at a wavelength of 280 nm. Eluents are channeled into a reaction coil and mixed with DTNB to form 5-thio-2-nitrobenzoic acid (TNB). Thiol concentration is calculated using absorption at 412 nm...
April 18, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28431324/achievable-separation-performance-and-analysis-time-in-current-liquid-chromatographic-practice-for-monoclonal-antibody-separations
#3
Szabolcs Fekete, Jean-Luc Veuthey, Davy Guillarme
The separation performance of a chromatographic system is often described in terms of column efficiency and peak capacity. Thanks to the new developments in column technology over the past few years, the achievable peak capacity drastically improved and the analysis time can be significantly shortened. Indeed, highly efficient wide-pore reversed-phase (RPLC) materials packed with small fully porous and superficially porous particles can be successfully used for the analytical characterization of therapeutic proteins...
April 12, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28430648/radioimmunotherapy-for-cd133-colonic-cancer-stem-cells-inhibits-tumor-development-in-nude-mice
#4
Dinghu Weng, Xueyan Jin, Saimei Qin, Xiaoli Lan, Chong Chen, Xun Sun, Xianliang She, Changling Dong, Rui An
Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427296/predictors-of-response-to-therapy-with-omalizumab-in-patients-with-severe-allergic-asthma-a-real-life-study
#5
Maria Kallieri, Andriana I Papaioannou, Evgenia Papathanasiou, Polyxeni Ntontsi, Spyridon Papiris, Stelios Loukides
INTRODUCTION: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. METHODS: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center...
April 21, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28426751/the-role-of-microsporidian-polar-tube-protein-4-ptp4-in-host-cell-infection
#6
Bing Han, Valérie Polonais, Tatsuki Sugi, Rama Yakubu, Peter M Takvorian, Ann Cali, Keith Maier, Mengxian Long, Matthew Levy, Herbert B Tanowitz, Guoqing Pan, Frédéric Delbac, Zeyang Zhou, Louis M Weiss
Microsporidia have been identified as pathogens that have important effects on our health, food security and economy. A key to the success of these obligate intracellular pathogens is their unique invasion organelle, the polar tube, which delivers the nucleus containing sporoplasm into host cells during invasion. Due to the size of the polar tube, the rapidity of polar tube discharge and sporoplasm passage, and the absence of genetic techniques for the manipulation of microsporidia, study of this organelle has been difficult and there is relatively little known regarding polar tube formation and the function of the proteins making up this structure...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28425076/monoclonal-gammopathy-of-renal-significance-mgrs-the-characteristics-and-significance-of-a-new-meta-entity
#7
REVIEW
Mariana Ciocchini, Jorge Arbelbide, Carlos G Musso
Monoclonal gammopathy of renal significance (MGRS) is a new nosological group of entities (meta-entity) defined in 2012, whose pathogenesis depends on monoclonal immunoglobulins (Ig) secreted by low-grade lymphoproliferative disorders, which belong to M-protein-related diseases. Renal damage is the result of monoclonal Ig deposit or its activity as autoantibodies, which can compromise any nephronal area. MGRS does not include kidney diseases produced by high-grade lymphoproliferative disorders as well as those whose pathogenesis are independent of monoclonal Ig (such as drug toxicity or metabolic disorders)...
April 19, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28423045/characterization-of-antennal-sensilla-larvae-morphology-and-olfactory-genes-of-melipona-scutellaris-stingless-bee
#8
Washington João de Carvalho, Patrícia Tieme Fujimura, Ana Maria Bonetti, Luiz Ricardo Goulart, Kevin Cloonan, Neide Maria da Silva, Ester Cristina Borges Araújo, Carlos Ueira-Vieira, Walter S Leal
There is growing evidence in the literature suggesting that caste differentiation in the stingless bee, Melipona scutellaris, and other bees in the genus Melipona, is triggered by environmental signals, particularly a primer pheromone. With the proper amount of food and a chemical stimulus, 25% of females emerge as queens, in agreement with a long-standing "two loci/two alleles model" proposed in the 1950s. We surmised that these larvae must be equipped with an olfactory system for reception of these chemical signals...
2017: PloS One
https://www.readbyqxmd.com/read/28422167/biotin-transfer-from-a-trifunctional-crosslinker-for-identification-of-cell-surface-receptors-of-soluble-protein-ligands
#9
Tammy-Lynn Tremblay, Jennifer J Hill
Here we describe a novel crosslinker and its application as a biotin-transfer reagent to identify cell surface receptors of soluble protein ligands on live cells. This crosslinker contains three functional groups: an aldehyde-reactive aminooxy group, a sulfhydryl, and a biotin (ASB). It is readily synthesized via a 3-step addition reaction using standard solid-phase peptide synthesis methods and commercially available intermediates, allowing access to laboratories without specialized synthetic chemistry capabilities...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28422137/effective-in-vivo-therapeutic-igg-antibody-against-vp3-of-enterovirus-71-with-receptor-competing-activity
#10
Qiang Jia, Qingyong Ng, Wenjie Chin, Tao Meng, Vincent Tak Kwong Chow, Cheng-I Wang, Jimmy Kwang, Fang He
Passive immunization is an effective option for treatment against hand, foot and mouth disease caused by EV71, especially with cross-neutralizing IgG monoclonal antibodies. In this study, an EV71-specific IgG2a antibody designated 5H7 was identified and characterized. 5H7 efficiently neutralizes the major EV71 genogroups (A, B4, C2, C4). The conformational epitope of 5H7 was mapped to the highly conserved amino acid position 74 on VP3 capsid protein using escape mutants. Neutralization with 5H7 is mediated by the inhibition of viral attachment, as revealed by virus-binding and post-attachment assays...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421819/il-4-induces-the-il17rb-gene-transcription-in-monocytic-cells-with-coordinate-autocrine-il-25-signaling
#11
Nathaniel M Weathington, Shreya S Kanth, Qiaoke Gong, James Londino, Akihiko Hoji, Mauricio Rojas, John Trudeau, Sally Wenzel, Rama K Mallampalli
IL-25 and IL-4 signaling in the setting of infection or allergic responses can drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to mediate signaling through nuclear factor kappa B transcriptional activation. Despite the known coexistence of these two cytokines in the Type 2 inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb protein in human lung tissue culture, primary alveolar macrophages, and the THP-1 monocytic cell line...
April 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28421387/pharmacokinetics-of-monoclonal-antibodies-and-fc-fusion-proteins
#12
REVIEW
Liming Liu
There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1-2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life...
April 19, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28421368/recombinant-foot-and-mouth-disease-virus-fmdv-non-structural-protein-3a-fused-to-enhanced-green-fluorescent-protein-egfp-as-a-candidate-probe-to-identify-fmdv-infected-cattle-in-serosurveys
#13
Cecilia M Lotufo, Ingrid E Bergmann, Nora M Mattion, Maximiliano Wilda, Pablo R Grigera
Recombinant protein 3A-EGFP, a fusion construct between foot-and-mouth disease virus (FMDV) non-structural protein 3A and the enhanced green fluorescent protein (EGFP) was expressed in BL21-DE3 cells. The identity of the partially purified protein 3A-EGFP was confirmed by its reactivity with sera from cattle infected with FMDV and with a monoclonal antibody specific for FMDV-3ABC (MAb3H7) in Western blot assays. No reactivity was observed with sera from uninfected vaccinated animals. The performance of 3A-EGFP as an antigen in an indirect enzyme-linked immunosorbent assay (ELISA) was assessed and compared with that of a previously developed and validated capture ELISA that uses a 3ABC recombinant antigen (3ABC ELISA) and has been widely applied for serological surveys in Argentina...
April 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28421075/activation-of-adhesion-gpcr-emr2-adgre2-induces-macrophage-differentiation-and-inflammatory-responses-via-g%C3%AE-16-akt-mapk-nf-%C3%AE%C2%BAb-signaling-pathways
#14
Kuan-Yu I, Yi-Shu Huang, Ching-Hsun Hu, Wen-Yi Tseng, Chia-Hsin Cheng, Martin Stacey, Siamon Gordon, Gin-Wen Chang, Hsi-Hsien Lin
EMR2/ADGRE2 is a human myeloid-restricted adhesion G protein-coupled receptor critically implicated in vibratory urticaria, a rare type of allergy caused by vibration-induced mast cell activation. In addition, EMR2 is also highly expressed by monocyte/macrophages and has been linked to neutrophil migration and activation. Despite these findings, little is known of EMR2-mediated signaling and its role in myeloid biology. In this report, we show that activation of EMR2 via a receptor-specific monoclonal antibody promotes the differentiation of human THP-1 monocytic cell line and induces the expression of pro-inflammatory mediators, including IL-8, TNF-α, and MMP-9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28417905/analytical-criticalities-associated-to-different-immunological-methods-for-serum-free-light-chain-detection-in-plasma-cell-dyscrasias-a-description-of-particular-clinical-cases
#15
Rocco Sabatino, Antonio Perrone, Marco Cuomo, Sandra Liotti, Vittoria Barchiesi, Monica Cantile, Ernesta Cavalcanti
Current criteria for differential diagnosis of multiple myeloma (MM), Monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM) are included in the 2003 guidelines by the International Myeloma Working Group (IMWG). An updated version was then published in 2014, highlighting the importance of serum free light chain (sFLC) detection, as well as the κ/λ ratio as excellent indicators of clonality. At present, two commercial assays for sFLC quantification are available: the Freelite™ assay and the N-Latex assay...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28417626/production-and-characterization-of-monoclonal-antibody-against-recombinant-virus-coat-protein-cp42
#16
Naeimeh Shibaei, Jafar Majidi, Khadijeh Razavi, Ali Asghar Karkhane, Nemat Sokhandan-Bashir, Leili Aghebati-Maleki
There are many studies related to the production of a ELISA kit for diagnosing virus infections. However, production of most kits depends on purification of whole virus particles, which involves the use of costly equipment and reagents. The purpose of this study was to check out if the anti-CP42 antibodies could be used as a diagnostic assay for detection of Grapevine fanleaf Virus (GFLV). In this study, recombinant GFLV coat protein gene related to selected antigenic determinants was inserted into pET-28a bacterial expression vector and the construct (pET-28a CP42) was cloned into E...
February 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28417501/d-dimer-level-in-association-with-humoral-responses-negatively-correlates-with-survival-of-porcine-islet-grafts-in-non-human-primates-with-immunosuppression
#17
Hee Jung Kang, Haneulnari Lee, Eun Mi Park, Jong-Min Kim, Byoung-Hoon Min, Chung-Gyu Park
BACKGROUND: Several immunosuppression (IS) regimens achieve long-term graft survival in non-human primates (NHPs) after porcine islet transplantation (PITx), but their success rates vary. To understand the mechanism of graft loss, we investigated the relationships between graft survival and humoral or inflammatory responses for maintenance IS in NHPs after PITx. METHODS: Islets purified from adult wild-type pigs were intraportally transplanted into streptozotocin-induced diabetic rhesus monkeys...
April 18, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28416674/inducing-protein-aggregation-by-extensional-flow
#18
John Dobson, Amit Kumar, Leon F Willis, Roman Tuma, Daniel R Higazi, Richard Turner, David C Lowe, Alison E Ashcroft, Sheena E Radford, Nikil Kapur, David J Brockwell
Relative to other extrinsic factors, the effects of hydrodynamic flow fields on protein stability and conformation remain poorly understood. Flow-induced protein remodeling and/or aggregation is observed both in Nature and during the large-scale industrial manufacture of proteins. Despite its ubiquity, the relationships between the type and magnitude of hydrodynamic flow, a protein's structure and stability, and the resultant aggregation propensity are unclear. Here, we assess the effects of a defined and quantified flow field dominated by extensional flow on the aggregation of BSA, β2-microglobulin (β2m), granulocyte colony stimulating factor (G-CSF), and three monoclonal antibodies (mAbs)...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28416374/comparing-originator-biologics-and-biosimilars-a-review-of-the-relevant-issues
#19
REVIEW
Corrado Blandizzi, Pier Luigi Meroni, Giovanni Lapadula
PURPOSE: We provide a review of current knowledge on comparability between biosimilars and originator biologics in view of the continuous evolution occurring in this highly dynamic area. METHODS: English-language literature indexed in MEDLINE was explored, without time limits, to July 31, 2016, using the terms biosimilar, biotechnologic drug, biologic drug, monoclonal antibody, fusion protein, and anti-tumor necrosis factor. The reference lists of identified articles were examined carefully for additional pertinent publications...
April 14, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28416076/sweat-allergy-extrinsic-or-intrinsic
#20
REVIEW
Takaaki Hiragun, Makiko Hiragun, Kaori Ishii, Takanobu Kan, Michihiro Hide
Sweat is an exacerbation factor in atopic dermatitis (AD) in all age groups. A body core temperature elevation with sweating triggers cholinergic urticaria (CholU). We recently reported that AD symptoms are improved by tannic acid-containing spray, which suppresses the basophil histamine release induced by semi-purified sweat antigen in vitro, and by showering, which removes antigens in sweat from the skin surface. Sweat contains small amount of proteins including proteases, protease inhibitors, and anti-microbial peptides...
March 9, 2017: Journal of Dermatological Science
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