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Tomoyuki Moriyama, Dai Kakiuchi, Luigi Grasso, David L Hutto, Danielle Fernando, Charles Schweizer
Farletuzumab is a humanized monoclonal antibody targeting human folate receptor alpha, which is being developed as an anti-cancer drug. A non-human primate reproductive study was conducted to evaluate whether it could cause any embryonic or fetal abnormalities. Farletuzumab was administered intravenously to pregnant cynomolgus monkeys (n = 16/group) at doses of 0 or 67.5 mg/kg once weekly during gestation day (GD) 20 through 97. C-section was performed on GD100 ± 2, and fetuses were evaluated for morphologic (external, visceral and skeletal) effects...
June 18, 2018: Reproductive Toxicology
Breanna Sheahan, Christopher M Dekaney
No abstract text is available yet for this article.
2018: Cellular and Molecular Gastroenterology and Hepatology
Nicholas R Smith, John R Swain, Paige S Davies, Alexandra C Gallagher, Michael S Parappilly, Catherine Z Beach, Philip R Streeter, Ian A Williamson, Scott T Magness, Melissa H Wong
Background & Aims: Continual renewal of the intestinal epithelium is dependent on active- and slow-cycling stem cells that are confined to the crypt base. Tight regulation of these stem cell populations maintains homeostasis by balancing proliferation and differentiation to support critical intestinal functions. The hierarchical relation of discrete stem cell populations in homeostasis or during regenerative epithelial repair remains controversial. Although recent studies have supported a model for the active-cycling leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)+ intestinal stem cell (ISC) functioning upstream of the slow-cycling B lymphoma Mo-MLV insertion region 1 homolog (Bmi1)-expressing cell, other studies have reported the opposite relation...
2018: Cellular and Molecular Gastroenterology and Hepatology
Ricardo L Pereira, Isis C Nascimento, Ana P Santos, Isabella E Y Ogusuku, Claudiana Lameu, Günter Mayer, Henning Ulrich
Although the term 'cancer' was still over two thousand years away of being coined, the first known cases of the disease date back to about 3000BC, in ancient Egypt. Five thousand years later, still lacking a cure, it has become one of the leading causes of death, killing over half a dozen million people yearly. So far, monoclonal antibodies are the most successful immune-therapy tools when it comes to fighting cancer. The number of clinical trials that use them has been increasing steadily during the past few years, especially since the Food and Drug Administration greenlit the use of the first immune-checkpoint blockade antibodies...
June 1, 2018: Oncotarget
Aafke Creemers, Eva A Ebbing, Gerrit K J Hooijer, Lisanne Stap, Rajni A Jibodh-Mulder, Susanne S Gisbertz, Mark I van Berge Henegouwen, Maurits L van Montfoort, Maarten C C M Hulshof, Kausilia K Krishnadath, Martijn G H van Oijen, Maarten F Bijlsma, Sybren L Meijer, Hanneke W M van Laarhoven
Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome...
June 1, 2018: Oncotarget
Jiasen Xie, Zishan Zhou, Shunchang Jiao, Xiaokun Li
A chimeric antigen receptor (CAR) is a type of fusion protein that comprises an antigen-recognition domain and signaling domains. In the present study, a programmed death-ligand 1 (PD-L1)-specific CAR, comprised of a single-chain variable fragment (scFv) derived from a monoclonal antibody, co-stimulatory domains of cluster of differentiation (CD) 28 and 4-1BB and a T-cell-activation domain derived from CD3ζ, was designed. The construction was cloned and packaged into the lentiviral vector pLVX. Flow cytometry confirmed that peripheral blood mononuclear cells were efficiently transduced and that the CAR was successfully expressed on T cells...
July 2018: Oncology Letters
Bo Zhang, Chenyan Fang, Dehou Deng, Liang Xia
As targeted drug therapy is increasingly applied in the treatment of colon cancer, understanding and managing the adverse reactions of patients is becoming increasingly important. The present review examines the mechanisms of and adverse reactions to the most commonly used targeted drugs for colon cancer, and discusses methods of coping with these adverse reactions. Approved targeted drugs for metastatic colon cancer include monoclonal antibodies targeting vascular endothelial growth factor (VEGF), including bevacizumab, ziv-aflibercept and regorafenib, and monoclonal antibodies targeting epithelial growth factor receptor (EGFR), including cetuximab and panitumumab...
July 2018: Oncology Letters
Jiansheng Lu, Rong Wang, Binghui Xia, Yunzhou Yu, Xiaowei Zhou, Zhixin Yang, Peitang Huang
The incidence of dengue virus (DENV) infections has been escalating in tropical and subtropical countries, but there are still no effective therapeutic options. In the present study, a DENV-1-specific human monoclonal antibody (HMAb), 1G5, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of dengue patients was found to have potent neutralization activity against serotype 1 DENV (DENV-1). Its neutralization activity against DENV-2 was not as strong, and it was almost absent for DENV-3 and DENV-4...
2018: Frontiers in Microbiology
Pablo F Barcelona, Alba Galan, Hinyu Nedev, Yifan Jian, Marinko V Sarunic, H Uri Saragovi
Many neurodegenerative retinal diseases are treated with monoclonal antibodies (mAb) delivered by invasive intravitreal injection (IVT). In Diabetic Retinopathy there is a scarcity of effective agents that can be delivered using non-invasive methods, and there are significant challenges in the validation of novel therapeutic targets. ProNGF represents a potential novel target, and IVT administration of a function-blocking anti-proNGF mAb is therapeutic in a mouse model of DR. We therefore compared invasive IVT to less invasive systemic intravenous (IV) and local subconjunctival (SCJ) administration, for therapy of Diabetic Retinopathy...
2018: PloS One
Eric M Mucker, Suzanne E Wollen-Roberts, Adrienne Kimmel, Josh Shamblin, Darryl Sampey, Jay W Hooper
Concerns regarding outbreaks of human monkeypox or the potential reintroduction of smallpox into an immunological naïve population have prompted the development of animal models and countermeasures. Here we present a marmoset model of monkeypox and smallpox disease utilizing a relevant poxvirus via a natural exposure route. We found that 1000 plaque forming units (PFU) of Monkeypox virus was sufficient to recapitulate smallpox disease, to include an incubation period of approximately 13 days, followed by the onset of rash, and death between 15 and 17 days...
June 21, 2018: PLoS Neglected Tropical Diseases
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant
OBJECTIVE: Transmission of HIV-1 involves a bottleneck in which generally a single HIV-1 variant from a diverse viral population in the transmitting partner establishes infection in the new host. It is still unclear to what extent this event is driven by specific properties of the transmitted viruses or the result of a stochastic process. Our study aimed to better characterize this phenomenon and define properties shared by transmitted viruses. DESIGN: We compared antigenic and functional properties of envelope glycoproteins of viral variants found during primary infection in 27 patients belonging to eight transmission chains...
June 20, 2018: AIDS
Pinar Incel Uysal, Onder Bozdogan, Ahmet Atilan, Basak Yalcin
We report a juvenile case of mycosis fungoides with prominent follicular mucinosis (FM). The patient was a 9-year old boy who presented with a 2-month history of enlarging alopecic patch with fine scales on the scalp. Dermatologic examination revealed orange-tan slightly palpable plaques with follicular prominence on his trunk. The patient and his family were not aware of these asymptomatic truncal plaques. Histopathologic examination of both-scalp and trunk-lesions revealed folliculotropic lymphocytic infiltration with mucin...
January 23, 2018: American Journal of Dermatopathology
A V Sidorin, A Yu Abrosimov, T I Rogunovich, P O Rumyantsev, K S Nizhegorodova, P A Isaev, A P Shinkarkina, S Yamasita, V A Saenko
The somatic mutation in BRAFT1799A (BRAFV600E ), the data on the prognostic role of which are contradictory, is one of the most common molecular genetic abnormalities in the cells of papillary thyroid carcinoma (PTC). OBJECTIVE: To investigate the association of the immunoexpression of mutant BRAF in PTC with different morphological characteristics and long-term treatment results in patients. MATERIAL AND METHODS: Information on inpatients with PTC was obtained from the database of the Pathology Department, A...
2018: Arkhiv Patologii
Daniele Raggi, Andrea Necchi, Patrizia Giannatempo
Nivolumab is a fully human monoclonal antibody blocking PD-1 with demonstrated effectiveness against metastatic urothelial carcinoma. In this review, we describe the pharmacological properties of nivolumab and the treatment of metastatic urothelial carcinoma with this checkpoint inhibitor after the failure of first-line platinum-based chemotherapy. Cancer immunotherapy by checkpoint inhibition offers potential to prolong patient survival with well manageable toxicity although serious immune-related adverse events may occur...
June 21, 2018: Future Oncology
Darlene A Pena, Denise M V Pacheco, Paulo S L Oliveira, Maria J M Alves, Deborah Schechtman
The protein kinase C (PKC) family of serine/ threonine kinases has been shown to play active roles as either suppressors or promoters of carcinogenesis in different types of tumors. Using antibodies that preferentially recognize the active conformation of classical PKCs (cPKCs), we have previously shown that in breast cancer samples the expression levels of cPKCs were similar in estrogen receptor-positive (ER+ ) as compared to triple-negative tumors; however, the levels of active cPKCs were different. Determining the activation status of PKCs and other kinases in tumors may thus aid therapeutic decisions...
June 2018: Current Protocols in Chemical Biology
Philip J Titcombe, Gustaf Wigerblade, Natalie Sippl, Na Zhang, Anna K Shmagel, Peter Sahlström, Yue Zhang, Laura O Barsness, Yogita Ghodke-Puranik, Azar Baharpoor, Monika Hansson, Lena Israelsson, Karl Skriner, Timothy B Niewold, Lars Klareskog, Camilla I Svensson, Khaled Amara, Vivianne Malmström, Daniel L Mueller
OBJECTIVE: Anti-citrullinated protein antibodies (ACPA) have proven highly useful as biomarkers in rheumatoid arthritis (RA). However, the composition and functionality of the associated autoreactive B cell repertoire have not been directly assessed. We aimed to selectively investigate citrullinated autoantigen-specific B cell receptors (BCRs) involved in RA and initiate studies on their pathogenicity. METHODS: A University of Minnesota ACPA+ RA cohort (n = 89 subjects) provided blood samples...
June 21, 2018: Arthritis & Rheumatology
S Khalilieh, A Hussain, D Montgomery, V Levine, P M Shaw, I Bodrug, L Mekokishvili, C Bailey-Smith, X S Glasgow, A Cheng, M Martinho, M Iwamoto
AIMS: Tildrakizumab, an interleukin (IL)-23 inhibitor, is indicated for the treatment of moderate to severe chronic plaque psoriasis. Although tildrakizumab is not metabolized by, and does not alter, cytochrome P450 (CYP) expression in vitro, clinically-significant pharmacokinetic effects through changes in systemic inflammation, which alters CYP metabolism, have been well documented. At the time of study conduct, the effect of modulation of inflammation/cytokines, including IL-23 inhibition with tildrakizumab, on CYP metabolism, and therefore the potential for disease-drug interactions, in psoriasis patients was unknown...
June 21, 2018: British Journal of Clinical Pharmacology
Cornelius F Waller, Apinya Vutikullird, Tracey E Lawrence, Andrew Shaw, Mark Shiyao Liu, Mark Baczkowski, Rajiv Sharma, Abhijit Barve, Parag Goyal, Charles Donnelly, Nilanjan Sengupta, Eduardo J Pennella
AIMS: Trastuzumab is a humanized monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2) oncoprotein and is an effective therapy for HER2-overexpressing breast cancer. MYL-1401O is a trastuzumab biosimilar. Here, we report results from a phase 1 study that investigated bioequivalence among MYL-1401O, reference EU-trastuzumab, and US-trastuzumab. METHODS: This single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study was conducted in healthy adult male volunteers...
June 21, 2018: British Journal of Clinical Pharmacology
Teruhiko Matsubara, Toshinori Sato, Takao Taki
"Glycoreplica peptides" are prepared using a phage display peptide library and monoclonal antibodies that recognize the carbohydrate epitopes of glycoconjugate antigens. The peptides obtained not only mimic the shapes of original glycoconjugate antigens but also have some of their functions. We herein describe how to identify the amino acid alignments of glycoreplica peptides using phage display selection against carbohydrate-binding proteins. Target-specific peptides and proteins may be selected from the large repertory of a peptide/protein library using phage display technology...
2018: Methods in Molecular Biology
Noriyuki Yuasa, Ikuo Kawashima
The antibody preparation method to the glycolipid is basically same to the method to the protein. However, because the immunogenicity of the carbohydrate moieties of glycolipid is generally low in the mouse, the development of the anti-glycolipid antibody using purified glycolipid as an immunogen was not yet established. Here, we describe a method using a purified ganglioside adsorbed onto Salmonella minnesota for the efficient production of an anti-ganglioside mouse monoclonal antibody that recognizes the carbohydrate moieties of the ganglioside...
2018: Methods in Molecular Biology
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