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Monoclonal antibody

Linlin Wang, Fang Zhang, Jian-Ying Cui, Liang Chen, Yue-Ting Chen, Bo-Wen Liu
Carcinoma‑associated fibroblasts (CAFs) are the major components of mesenchymal cells in the inflammatory tumor microenvironment. They are involved in epithelial‑mesenchymal transition (EMT) and chemotherapy resistance by directly contacting with cancer cells or secretory cytokines. In the present study, we examined the role of CAFs in the induction of EMT in ovarian cancer. Primary ovarian cancer cells, CAFs and normal fibroblasts (NFs) were isolated from fresh cancer tissue and cultured for immunohistochemistry studies...
May 2018: Oncology Reports
Octavia Ramayanti, Mitch Brinkkemper, Sandra A W M Verkuijlen, Leni Ritmaleni, Mei Lin Go, Jaap M Middeldorp
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA...
March 22, 2018: Cancers
Takafumi Ito, Jun Kurita, Koh-Ichiro Mori, Helle Frank Skall, Niels Lorenzen, Niccolò Vendramin, Nikolaj Gedsted Andersen, Katja Einer-Jensen, Niels Jørgen Olesen
Four major genotypes of viral haemorrhagic septicaemia virus (VHSV), which have been isolated from many marine and freshwater fish species, are known to differ in virulence. While fast and low-cost genotyping systems based on monoclonal antibodies (MAbs) have been developed for typing of VHSV virulence, there is a need for supplementing the knowledge. In particular, 2 field isolates from viral haemorrhagic septicaemia (VHS) outbreaks in sea-reared rainbow trout Oncorhynchus mykiss in Sweden, SE-SVA-14 and SE-SVA-1033 (both genotype Ib), have yielded contradictory reactions...
March 22, 2018: Diseases of Aquatic Organisms
Diego Luigi Cortinovis
In recent years immunotherapy has become a fundamental part of the treatment of many solid tumors, including non-small cell lung cancer (NSCLC). With the results of trials investigating the role of monoclonal antibodies against immuno-checkpoints in particular, today these drugs have become part of everyday clinical practice, even though many questions still remain unresolved (optimal duration of treatment, prognostic and predictive role of biomarkers, management of immuno-related toxicity). Here we report the case of our patient with diagnosis of metastatic lung adenocarcinoma "non oncogene driven" successfully treated in second line with nivolumab, analyzing the problems and the questions most frequently evidenced during treatment with these new molecules...
March 2018: Recenti Progressi in Medicina
Stephen T Keir, Vidyalakshmi Chandramohan, Carlee D Hemphill, Michael M Grandal, Maria Carlsen Melander, Mikkel W Pedersen, Ivan D Horak, Michael Kragh, Annick Desjardins, Henry S Friedman, Darell D Bigner
BACKGROUND: Sym004 is a mixture of two monoclonal antibodies (mAbs), futuximab and modotuximab, targeting non-overlapping epitopes on the epidermal growth factor receptor (EGFR). Previous studies have shown that Sym004 is more efficient at inducing internalization and degradation of EGFR than individual components, which translates into superior cancer cell inhibition. We investigated whether Sym004 induces removal of EGFRvIII and if this removal translates into tumor growth inhibition in hard-to-treat glioblastomas (GBMs) harboring the mutated, constitutively active EGFR variant III (EGFRvIII)...
March 21, 2018: Journal of Neuro-oncology
Hanny Al-Samkari, Rachael F Grace, Jean M Connors
Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder resulting in potentially life-threating systemic thrombotic microangiopathy due to production of antibodies directed against the von Willebrand factor-cleaving protease ADAMTS13. Typically managed with plasma exchange, glucocorticoids, and the first-generation anti-CD20 monoclonal antibody rituximab, patients with multiple relapses or refractory disease present unique management challenges. We describe a case of a young woman with multiple relapses of TTP despite standard therapy who was treated with ofatumumab, a second-generation anti-CD20 monoclonal antibody, after developing a severe hypersensitivity reaction to rituximab precluding its use...
March 21, 2018: Journal of Thrombosis and Thrombolysis
Michael Willis, Irmgard Leitner, Klaus Seppi, Maria Trieb, Georg Wietzorrek, Josef Marksteiner, Hans-Günther Knaus
In this study, we investigated the tissue expression levels, alpha subunit composition and distribution of Shaker-related voltage-dependent potassium Kv1 channels in human hippocampus by combining western blotting experiments, toxin autoradiography, in vivo radioligand binding studies, immunoprecipitation and immunohistochemistry. Tissue expression of Kv1.1 and Kv1.2 α-subunits in human post-mortem brain tissue was confirmed in immunoblot analysis using a panel of specific monoclonal and polyclonal antibodies...
March 21, 2018: Brain Structure & Function
Weihsu C Chen, Christopher M Murawsky
Therapeutic molecules derived from antibodies have become a dominant class of drugs used to treat human disease. Increasingly, therapeutic antibodies are discovered using transgenic animal systems that have been engineered to express human antibodies. While the engineering details differ, these platforms share the ability to raise an immune response that is comprised of antibodies with fully human idiotypes. Although the predominant transgenic host species has been mouse, the genomes of rats, rabbits, chickens, and cows have also been modified to express human antibodies...
2018: Frontiers in Immunology
Weon Sup Lee, Sang Ryeol Shim, Seon Young Lee, Jin San Yoo, Sung Kweon Cho
Background: VEGF is a highly selective mitogen that serves as the central regulator of tumor angiogenesis by mediating endothelial proliferation, permeability, and survival. Tanibirumab (TTAC-0001) is a fully human IgG1 monoclonal antibody derived from a fully human naïve single-chain variable fragment (ScFv) phage library that was developed to inhibit the effects of VEGF in the treatment of solid tumors, especially those of the brain. Methods: In the present study, we conducted intravenous pharmacokinetic studies of TTAC-0001 in mice, rats, and cynomolgus monkeys...
2018: Drug Design, Development and Therapy
Tatiana A Karakasheva, George A Dominguez, Ayumi Hashimoto, Eric W Lin, Christopher Chiu, Kate Sasser, Jae W Lee, Gregory L Beatty, Dmitry I Gabrilovich, Anil K Rustgi
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a population of immature immune cells with several protumorigenic functions. CD38 is a transmembrane receptor-ectoenzyme expressed by MDSCs in murine models of esophageal cancer. We hypothesized that CD38 could be expressed on MDSCs in human colorectal cancer (CRC), which might allow for a new perspective on therapeutic targeting of human MDSCs with anti-CD38 monoclonal antibodies in this cancer. METHODS: Blood samples were collected from 41 CRC patients and 8 healthy donors, followed by peripheral blood mononuclear cell (PBMC) separation...
March 22, 2018: JCI Insight
Denise C Hsu, Piyanate Sunyakumthorn, Matthew Wegner, Alexandra Schuetz, Decha Silsorn, Jacob D Estes, Claire Deleage, Khamis Tomusange, Samir K Lakhashe, Ruth M Ruprecht, Eric Lombardini, Rawiwan Im-Erbsin, Yanin Kuncharin, Yuwadee Phuang-Ngern, Dutsadee Inthawong, Weerawan Chuenarom, Robin Burke, Merlin L Robb, Lishomwa C Ndhlovu, Jintanat Ananworanich, Victor Valcour, Robert J O'Connell, Serena Spudich, Nelson L Michael, Sandhya Vasan
Studies utilizing highly pathogenic simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) have largely focused on the immunopathology of the central nervous system (CNS) during end-stage neuro AIDS and SIV encephalitis. However, this may not model pathophysiology in earlier stages of infection. In this non-accelerated SHIV model, plasma SHIV RNA levels and peripheral blood and colonic CD4 T+ cell counts mirrored early HIV infection in humans. At 12 weeks post infection, cerebrospinal fluid (CSF) detection of SHIV RNA and elevations in IP-10 and MCP-1 reflected a discrete neurovirologic process...
March 21, 2018: Journal of Virology
Ricardo García-Muñoz, Lorea Aguinaga, Jesus Feliu, Judit Anton-Remirez, Lorena Jorge-Del-Val, Andrea Casajús-Navasal, María José Nebot-Villacampa, Isabel Daroca-Fernandez, Elena Domínguez-Garrido, Pilar Rabasa, Carlos Panizo
AIM: Obinutuzumab induces NK cell antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: Investigate the effects on the human immune system after obinutuzumab monotherapy treatment in patients with chronic lymphocytic leukemia (CLL). METHOD: To evaluate these effects, we analyzed the distribution of CD4+ and CD8+ T cells, B cells and NK cells in the peripheral blood of eight CLL patients who were treated with obinutuzumab in monotherapy...
March 1, 2018: Immunotherapy
Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, David E Volk, Takemi Tanaka
Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules...
March 19, 2018: Cancers
Yongao Xiong, Qiongyu Li, Muchena J Kailemia, Carlito B Lebrilla, Somen Nandi, Karen A McDonald
Kifunensine, a potent and selective inhibitor of class I α-mannosidases, prevents α-mannosidases I from trimming mannose residues on glycoproteins, thus resulting in oligomannose-type glycans. We report for the first time that through one-time vacuum infiltration of kifunensine in plant tissue, N-linked glycosylation of a recombinant protein transiently produced in whole-plants shifted completely from complex-type to oligomannose-type. Fc-fused capillary morphogenesis protein 2 (CMG2-Fc) containing one N -glycosylation site on the Fc domain, produced in Nicotiana benthamiana whole plants, served as a model protein...
March 17, 2018: International Journal of Molecular Sciences
Giovanni Ciccarelli, Saverio D'Elia, Michele De Paulis, Paolo Golino, Giovanni Cimmino
The role of low-density lipoproteins (LDLs) as a major risk factor for cardiovascular disease has been demonstrated by several epidemiological studies. The molecular basis for LDLs in atherosclerotic plaque formation and progression is not completely unraveled yet. Pharmacological modulation of plasma LDL-C concentrations and randomized clinical trials addressing the impact of lipid-lowering interventions on cardiovascular outcome have clearly shown that reducing plasma LDL-C concentrations results in a significant decrease in major cardiovascular events...
March 17, 2018: Diseases (Basel)
H Peeters, E Louis, F Baert, O Dewit, J C Coche, M Ferrante, G Lambrecht, A Colard, A Van Gossum, P Bossuyt, T Moreels, B Vander Cruyssen, A Gils, M De Vos
BACKGROUND AND STUDY AIMS: Anti-TNF monoclonal antibodies are a cornerstone in the treatment of Crohn's disease. Prospective data on switching from the subcutaneous and human adalimumab (ADM) to the intravenous and chimeric infliximab (IFX) are scarce. PATIENTS AND METHODS: In this prospective, observational, multicentre cohort study we included 21 patients with loss of response to ADM despite at least 4 consecutive weekly injections. Clinical response (CDAI drop≥70 points) and remission (CDAI≤150) were assessed after switching from ADM to IFX after 10 weeks, 6 and 12 months...
January 2018: Acta Gastro-enterologica Belgica
Benjamin B Kasten, Patsy G Oliver, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. There is a clinical need for effective, targeted therapy strategies that destroy both differentiated TNBC cells and TNBC cancer initiating cells (CICs), as the latter are implicated in the metastasis and recurrence of TNBC. Chondroitin sulfate proteoglycan 4 (CSPG4) is overexpressed on differentiated tumor cells and CICs obtained from TNBC patient specimens, suggesting that CSPG4 may be a clinically relevant target for the imaging and therapy of TNBC...
March 21, 2018: International Journal of Molecular Sciences
Robert M Stoekenbroek, John J P Kastelein
PURPOSE OF REVIEW: This review describes the pivotal role of genetic insights and technologies in the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the rapid development of PCSK9 inhibitors - a revolutionary new class of lipid-lowering agents. RECENT FINDINGS: PCSK9 was discovered as a the third gene implicated in familial hypercholesterolemia. Population genetics studies, enabled by technological advances, were instrumental in validating PCSK9 as a therapeutic target...
March 20, 2018: Current Opinion in Cardiology
Francesco Sparano, Michele Cavo, Pasquale Niscola, Tommaso Caravita, Fabio Efficace
PURPOSE: We performed a systematic review to quantify the amount of evidence-based data available on patient-reported outcomes (PRO) in Relapsed/Refractory Multiple Myeloma (RRMM) patients and to examine the added value of such studies in supporting clinical decision-making. METHODS: We conducted a search in PubMed/Medline and the Cochrane Library to identify studies published between January 1990 and May 2017. All studies, regardless of the design, including patients with RRMM and also evaluating PRO were considered...
March 20, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Thomas D'huys, Sandra Claes, Tom Van Loy, Dominique Schols
Chemokine receptors CCR5 and CXCR4 are considered the main coreceptors for initial HIV infection, replication and transmission, and subsequent AIDS progression. Over the years, other chemokine receptors, belonging to the family of G protein-coupled receptors, have also been identified as candidate coreceptors for HIV entry into human host cells. Amongst them, CXCR7, also known as atypical chemokine receptor 3 (ACKR3), was suggested as a coreceptor candidate capable of facilitating both HIV-1 and HIV-2 entry in vitro ...
March 2018: Heliyon
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