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Monoclonal antibodie

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
Kimihiro Nishino, Sayaka Koda, Naoya Kataoka, Shinji Takamatsu, Miyako Nakano, Shun Ikeda, Yuka Kamamatsu, Koichi Morishita, Kenta Moriwaki, Hidetoshi Eguchi, Eiko Yamamoto, Fumitaka Kikkawa, Yasuhiko Tomita, Yoshihiro Kamada, Eiji Miyoshi
We previously found that the serum level of fucosylated haptoglobin (Fuc-Hpt) was significantly increased in pancreatic cancer patients. To delineate the mechanism underlying this increase and develop a simple detection method, we set out to generate a monoclonal antibody (mAb) specific for Fuc-Hpt. After multiple screenings by enzyme-linked immunosorbent assay (ELISA), a 10-7G mAb was identified as being highly specific for Fuc-Hpt generated in a cell line as well as for Hpt derived from a pancreatic cancer patient...
February 27, 2018: Oncotarget
Jean-David Fumet, Aurélie Bertaut, Leila Bengrine, Patricia Lapierre, Julie Vincent, François Ghiringhelli, Nicolas Falvo
Background: Bevacizumab is a recombinant humanized monoclonal immunoglobulin G1 antibody targeting VEGF-A. It is currently used with chemotherapy as the first- or second-line therapy in metastatic colorectal cancer. Previous studies have showed that anti-angiogenic agents decrease capillary density. We evaluated the link between decreased capillary density and the response to bevacizumab-based chemotherapy. Results: Overall, 43 patients with metastatic colorectal cancer treated with first-line bevacizumab-based chemotherapy were enrolled...
February 27, 2018: Oncotarget
David M Hyman, Naiyer A Rizvi, Ronald B Natale, Deborah K Armstrong, Michael J Birrer, Lawrence Recht, Efrat Dotan, Vicky Makker, Thomas J Kaley, Denison Kuruvilla, Matthew Gribbin, Jennifer McDevitt, Dominic W Lai, Mohammed M Dar
PURPOSE: This first-in-human study aimed to determine the maximum tolerated dose (MTD) and safety of MEDI3617, a selective anti-angiopoietin-2 (Ang2) monoclonal antibody, alone and combined with bevacizumab or cytotoxic chemotherapy. Experimental Design: This phase I/Ib, multicenter, open-label, dose escalation and dose expansion study evaluated patients with advanced solid tumors. Patients received intravenous MEDI3617 as monotherapy (5-1500 mg every 3 weeks [Q3W]) or with bevacizumab every 2 weeks (Q2W) or Q3W, weekly paclitaxel, or carboplatin plus paclitaxel Q3W...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hope S Rugo, Jean-Pierre Delord, Seock-Ah Im, Patrick A Ott, Sarina A Piha-Paul, Phillipe L Bedard, Jasgit Sachev, Christophe Le Tourneau, Emilie M J van Brummelen, Andreea Varga, Roberto Salgado, Sherene Loi, Sanatan Saraf, Dina Pietrangelo, Vassiliki Karantza, Antoinette R Tan
PURPOSE: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor‒positive (ER+)/human epidermal growth factor receptor 2-negative (HER2- ) advanced breast cancer with programmed death ligand 1‒positive (PD-L1‒positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. EXPERIMENTAL DESIGN: Patients with ER+/HER2- advanced breast cancer with PD-L1‒positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sara Clemenza, Flavia Sorbi, Ivo Noci, Tommaso Capezzuoli, Irene Turrini, Carlo Carriero, Nicolò Buffi, Massimiliano Fambrini, Felice Petraglia
Endometriosis is a chronic disease, and a lifelong management plan should be developed by using pharmacological treatment and surgical procedures. The pathogenesis of endometriosis is complicated and has not been definitively established. The mechanisms involved are numerous, and their understanding is constantly evolving. Currently, the first-line drugs act by blocking ovarian function, creating an hypoestrogenic environment. The blockade of estrogen secretion and receptor activity and the activation of progesteron receptors are the main target of several current drugs, as well as those under development...
February 15, 2018: Best Practice & Research. Clinical Obstetrics & Gynaecology
Sehar Qudsia, Siva B Merugu, Hitesh B Mangukiya, Negi Hema, Zhenghua Wu, Dawei Li
Antibody display libraries have become a popular technique to screen monoclonal antibodies for therapeutic purposes. An important aspect of display technology is to generate an optimization library by changing antibody affinity to antigen through mutagenesis and screening the high affinity antibody. In this study, we report a novel lentivirus display based optimization library antibody in which Agtuzumab scFv is displayed on cell membrane of HEK-293T cells. To generate an optimization library, hotspot mutagenesis was performed to achieve diverse antibody library...
March 17, 2018: Biochemical and Biophysical Research Communications
Jiaqing Luo, Hongchao Sun, Xianfeng Zhao, Suhua Wang, Xunhui Zhuo, Yi Yang, Xueqiu Chen, Chaoqun Yao, Aifang Du
The immunochromatographic test (ICT) is a convenient and low-cost method that can rapidly obtain results (10 min) under normal conditions. In this study, we established an ICT assay with two monoclonal antibodies: TgSAG3-3A7 and TgSAG3-4D5 based on the conserved protein of TgSAG3 that can be expressed in all the infective stages of T. gondii. 20 nm gold particles were prepared and conjugated with TgSAG3-3A7 MAb at the concentration of 12.5 μg/mL. TgSAG3-4D5 MAb were used as the capture antibody because of its higher affinity tested by ELISA...
March 15, 2018: Veterinary Parasitology
Qin Wang, Luisette Delva, Paul H Weinreb, Robert B Pepinsky, Danielle Graham, Elvana Veizaj, Anne E Cheung, Weiping Chen, Ivan Nestorov, Ellen Rohde, Robin Caputo, Geoffrey M Kuesters, Tonika Bohnert, Liang-Shang Gan
BACKGROUND: Many studies have focused on the challenges of small molecule uptake across the blood-brain barrier, whereas few in-depth studies have assessed the challenges with the uptake of antibodies into the central nervous system (CNS). In drug development, cerebrospinal fluid (CSF) sampling is routinely used as a surrogate for assessing CNS drug exposure and biomarker levels. In this report, we have studied the kinetic correlation between CSF and serum drug concentration-time profiles for five humanized monoclonal antibodies in rats and cynomolgus monkeys and analyzed factors that affect their CSF exposure...
March 20, 2018: Fluids and Barriers of the CNS
Mariola Śliwińska-Mossoń, Stanisław Milnerowicz, Halina Milnerowicz
The present study was conducted to ascertain how cigarette smoke affects the exocrine-endocrine interactions of the human pancreas with diabetes mellitus secondary to pancreatic diseases (type 3c). Blood has been collected from smoking and non-smoking healthy individuals as well as from patients with diagnosed chronic pancreatitis and diabetes type 3c. The concentrations of interleukin-6, endothelin-1 and insulin in the plasma were determined by enzyme-linked immunosorbent assay (ELISA) tests. The activities of amylase and lipase in the serum, as well as the lipid profile, creatinine, uric acid and urea concentrations, were measured using colorimetric methods...
March 1, 2018: Diabetes & Vascular Disease Research
Xiangzhi Meng, Thomas Kaever, Bo Yan, Paula Traktman, Dirk M Zajonc, Bjoern Peters, Shane Crotty, Yan Xiang
Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy...
March 17, 2018: Virology
Hiroki Wakabayashi, Takahiko Hamaguchi, Nobuto Nagao, Sho Kato, Takahiro Iino, Tomoki Nakamura, Akihiro Sudo
BACKGROUND: Interleukin-6 (IL-6) is a potent inflammatory cytokine that appears to play a key role in cancer growth and metastasis. In the present study, the effects of IL-6 receptor (IL-6R) on breast cancer aggressiveness and bone metastases were investigated. METHODS: MDA-MB-231 (MDA-231) cells were treated in the presence or absence of anti-human IL-6 receptor (IL-6R) monoclonal antibody and examined with respect to cell survival. The expressions of signal transducer and activator of transcription 3 (Stat3), vascular endothelial growth factor (VEGF), and receptor activator of NF-κB (RANK) were analyzed by SDS-PAGE and immunoblotting...
March 19, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Philip R Holland, Peter J Goadsby
Migraine is a highly prevalent, severe, and disabling neurological condition with a significant unmet need for effective acute therapies. Patients (~50%) are dissatisfied with their currently available therapies. Calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide involved in the pathophysiology of migraines. As reviewed in this manuscript, a number of small molecule antagonists of the CGRP receptor have been developed for migraine therapy. Incredibly, the majority of the clinical trials conducted have proven positive, demonstrating the importance of this signalling pathway in migraine...
March 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Taner Demirer
Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research...
March 20, 2018: Advances in Experimental Medicine and Biology
Takeshi Yuasa, Shinji Urakami, Junji Yonese
Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice...
March 20, 2018: International Journal of Clinical Oncology
Alessandro S Zagami
PURPOSE OF REVIEW: To review recent studies outlining the management of refractory primary headache patients, including emerging therapies such as neuromodulation. This includes both noninvasive and invasive neuromodulation techniques. Recent studies on the management of medication overuse headache were also reviewed. RECENT FINDINGS: There is no consensus as yet on the definitions of refractory chronic migraine and chronic cluster headache although there is broad agreement on some aspects of these terms...
March 19, 2018: Current Pain and Headache Reports
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