Development and validation of a (RP)UHPLC-UV-(HESI/Orbitrap)MS method for the identification and quantification of mixtures of intact therapeutical monoclonal antibodies using a monolithic column

Publication date: Available online 17 July 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Raquel Pérez-Robles, Luis Cuadros-Rodríguez, Antonio Salmerón-García, Natalia NavasAbstractMonoclonal antibodies (mAbs) are one of the most important types of biopharmaceutics and have proved enormously successful in the treatment of cancers and autoimmune diseases. In this paper, we present a fast, straightforward reversed phase (RP)UHPLC-UV-(HESI/Orbitrap) MS method for the separation and identification of five of the most commonly used mAbs, i.e. bevazizumab (BEV), cetuximab (CTX), infliximab (INF), rituximab (RTX) and trastuzumab (TTZ) in mixtures. The RP mAbs separation was performed in a divinylbenzene-based monolithic column, after statistical design of the experiments with a novel approach for optimizing chromatographic conditions called the heteroscedasticity function. Results led us to split the initial mixture of five mAbs into two mixtures with four mAbs each, one containing RTX and the other TTZ. The method was validated for quantification using the signal from the UV detector and identification by (HESI-Orbitrap)MS. Direct MS characterization of the intact isoform profile of each mAb was also obtained. Advantages and disadvantages of the use of trifluoroacetic acid or formic acid as ion pairing agents for mass spectrometric analysis and chromatographic separation are discussed. Validation was performed using an internal p...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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Conclusion: This review is focused not only on the mechanism by which the immune system protects us but also on the ways in which it can inflict the body and how to modulate it with therapy. Thus, understanding the interaction of a tumor with the immune system provides insights into mechanisms that can be utilized to elicit anti-tumor immune responses. Here, we have recapitulated the function of the tumor microenvironment and immune checkpoints.
Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology Source Type: research
Conclusion: Here we discuss the major implications of these findings for the association between microorganisms and cancer, and also between some immune pathologies, like autoimmune diseases, and cancer.
Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology Source Type: research
Publication date: Available online 14 November 2019Source: Pharmacological ResearchAuthor(s): Mingxue Li, Dun Wang, Jianhua He, Lixia Chen, Hua LiAbstractB-cell lymphoma-extra large (Bcl-XL) is one of the anti-apoptotic proteins of the Bcl-2 family that is localized in the mitochondria. Bcl-XL is one of the key regulators of apoptosis that can also regulate other important cellular functions. Bcl-XL is overexpressed in many cancers, and its inhibitors have shown good therapeutic effects. Bcl-XL interacts with Beclin 1, a key factor regulating autophagy.Bcl-XL is essential for the survival of neurons and plays protective ro...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Authors: Cui XF, Cui XG, Leng N Abstract Papillary renal cell carcinoma (PRCC) accounts for about 10 percent of all renal cell carcinomas, and the prognosis is poor for people with advanced disease. Interleukin-20 receptor subunit beta (IL20RB) is a single-pass type I membrane protein of the type II cytokine receptor family and is related to the pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, glaucoma, vitiligo, rheumatoid arthritis, and inflammatory bowel disease. However, little has been reported on IL20RB with respect to cancer, especially in PRCC. Thus, we performed this study...
Source: Journal of Toxicologic Pathology - Category: Toxicology Tags: J Toxicol Pathol Source Type: research
Abstract The 2020 Annual Review Issue, "Preventing Disease in the 21st Century" was selected by the Editors-in-Chief of Pediatric Research to include a variety of disease entities that confront health-care practitioners entrusted to the care of infants and children. In keeping with this mandate, this article reviews the subject of epigenetics, which impacts pediatric research from bench to bedside. Epigenetic mechanisms exert their effects through the interaction of environment, various susceptibility genes, and immunologic development and include: (1) DNA methylation; (2) posttranslational modifications...
Source: Pediatric Research - Category: Pediatrics Authors: Tags: Pediatr Res Source Type: research
ConclusionsThis study suggests that the outcome after initial treatment of MALT lymphomas in the oromaxillofacial head and neck region is satisfactory and that this disease progresses slowly. The CR rate and PFS of localized lymphoma patients are better than those of disseminated lymphoma patients. Systemic treatment (chemotherapy or rituximab) may improve PFS in disseminated disease patients. MALT ‐IPI and Ann Arbor staging are independent prognostic factors.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Semin Liver Dis DOI: 10.1055/s-0039-3399562Neutrophil extracellular traps, or NETs, are heterogenous, filamentous structures which consist of extracellular DNA, granular proteins, and histones. NETs are extruded by a neutrophil in response to various stimuli. Although NETs were initially implicated in immune defense, subsequent studies have implicated NETs in a spectrum of disease processes, including autoimmune disease, thrombosis, and cancer. NETs also contribute to the pathogenesis of several common liver diseases, including alcohol-associated liver disease and portal hypertension. Although there is much interest in the...
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
Publication date: Available online 11 November 2019Source: MethodsAuthor(s): Jennifer I. Brown, Brent D.G. Page, Adam FrankelAbstractProtein arginine N-methyltransferases (PRMTs) are a family of 9 enzymes that catalyze mono- or di-methylation of arginine residues using S-adenosyl-L-methionine (SAM). Arginine methylation is an important post-translational modification that can regulate the activity and structure of target proteins. Altered PRMT activity can lead to a variety of health issues including neurodevelopmental disease, autoimmune disorders, cancer, and cardiovascular disease. Thus, developing a robust mechanistic ...
Source: Methods - Category: Molecular Biology Source Type: research
(Lund University) A research team at Lund University in Sweden has found the mechanism that controls the growth of B1-cells in mice. The findings, which may lead to a deeper understanding of certain forms of cancer and autoimmune diseases, was recently published in the journal Science Immunology.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Abstract In an editorial in an earlier issue of this journal, Johanson &Tinnerberg (1) expressed serious and well-founded concern over the large number of future occupational cancer cases that will result if exposures for a number of substances are not reduced below the so-called "binding occupational exposure limit values" (BOELV) issued by the EU (2). The balance between what is perceived as possible to comply with and the foreseeable health gain when setting BOELV is further discussed in a letter to the Editor by Cherrie (3). This debate raises several important aspects of how to protect workers f...
Source: Scandinavian Journal of Work, Environment and Health - Category: Occupational Health Authors: Tags: Scand J Work Environ Health Source Type: research
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