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https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#1
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346585/maternal-vaccination-with-a-mono-component-pertussis-toxoid-vaccine-is-sufficient-to-protect-infants-in-a-baboon-model-of-whooping-cough
#2
Parul Kapil, James F Papin, Roman F Wolf, Lindsey I Zimmerman, Leslie D Wagner, Tod J Merkel
Background: Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at six to eight weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease...
January 15, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29346488/a-subretinal-cell-delivery-method-via-suprachoroidal-access-in-minipigs-safety-and-surgical-outcomes
#3
Marc D de Smet, Jessica L Lynch, Nadine S Dejneka, Michael Keane, I John Khan
Purpose: This study evaluated a new subretinal method for delivery of human or pig umbilical tissue-derived cells (hUTC or pUTC, respectively) using a novel subretinal injection cannula and suprachoroidal approach in Göttingen minipig eyes. hUTC (palucorcel) are currently under development for treating geographic atrophy in humans. Methods: Twenty-four Göttingen minipigs (divided into eight groups) were subretinally administered palucorcel, pUTC, or vehicle. In some cases, fluorescently labeled cells and vehicle were administered...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29346435/influenza-a-virus-hemagglutinin-glycosylation-compensates-for-antibody-escape-fitness-costs
#4
Ivan Kosik, William L Ince, Lauren E Gentles, Andrew J Oler, Martina Kosikova, Matthew Angel, Javier G Magadán, Hang Xie, Christopher B Brooke, Jonathan W Yewdell
Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#5
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29346076/ultrasensitive-electrochemical-immuno-sensing-platform-based-on-gold-nanoparticles-triggering-chlorpyrifos-detection-in-fruits-and-vegetables
#6
Anita Talan, Annu Mishra, Sergei A Eremin, Jagriti Narang, Ashok Kumar, Sonu Gandhi
Chlorpyrifos (chl) is an organophosphate pesticide extensively used in agriculture and highly toxic for human health. Fluorine doped tin-oxide (FTO) based electrochemical nanosensor was developed for chlorpyrifos detection with gold nanoparticles (AuNPs) and anti-chlorpyrifos antibodies (chl-Ab). AuNPs provides high electrical conductivity and specific resistivity, thus increases the sensitivity of immunoassay. High electrical conductivity of AuNPs reveals that it promotes the redox reaction for better cyclic voltammetry...
January 9, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29345964/immune-response-to-dengue-and-zika
#7
Annie Elong Ngono, Sujan Shresta
Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection...
January 18, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29345851/the-immunosuppressive-effects-of-cd4-cd25-regulatory-t-cells-on-dendritic-cells-in-patients-with-chronic-hepatitis-b
#8
Pei-Pei Zhou, Juan Xu, Ming-Jia Dai, Yin-Yue Shi, Gui-Ping Wu, Yuan Fang, Xue-Bing Yan
The characteristics and functions of CD4+ CD25+ regulatory T cells (Tregs) have been well defined in murine and human systems. However, the interaction or cross-talk between CD4+ CD25+ Tregs and dendritic cells (DCs) remains controversial. In this study, the effects of chronic hepatitis B (CHB) CD4+ CD25+ Tregs on the maturation and function of monocyte-derived DCs were examined. The results showed that CD4+ CD25+ render the DCs inefficient as antigen-presenting cells (APCs) despite prestimulation with CD40 ligand...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345369/memory-b-cell-heterogeneity-remembrance-of-things-past
#9
REVIEW
Gretchen Harms Pritchard, Marion Pepper
B cells that persist for long periods of time after antigen encounter exist as either antibody-producing plasma cells (long-lived plasma cells, LLPCs) that reside primarily in the bone marrow or rapidly responsive memory B cells (MBCs) that reside in the spleen and circulation. Although LLPCs are thought to be non-responsive to a secondary infection, MBCs respond to subsequent infection through the production of antibody-secreting cells, formation of new germinal centers (GCs), and repopulation of the memory pool...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345363/effects-of-il-10-and-th-2-cytokines-on-human-m%C3%AF-phenotype-and-response-to-csf1r-inhibitor
#10
Leon P Pradel, Andreas Franke, Carola H Ries
Tumor-associated Mφs display a plastic phenotype that is regulated by the local tumor milieu. Gene expression analysis and functional characterization of Mφs exposed in vitro to individual cytokines aids to delineate the cross-talk between defined cytokines shaping the complex Mφ phenotype. Human monocyte-derived Mφs can be differentiated in vitro with the T helper cell type 2 response cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking antibody emactuzumab...
January 4, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345292/preparation-and-characterization-of-the-antibody-recognizing-amacr-inside-its-catalytic-center
#11
Boris V Popov, Gleb I Sutula, Nikolay S Petrov, Ximing J Yang
Alpha-methylacyl-CoA racemase (AMACR) catalyzes the β-oxidation of fatty acids and is overexpressed in carcinomas in various organs, while its inactivation results in the inhibition of cancer growth. In the present study, we prepared and characterized 20 different mouse monoclonal antibodies against human AMACR. In the course of biopanning of a phage peptide commercial library against in-house prepared 6H9 and 2A5, and commercial 13H4 antibodies, 10 phage mimotopes recognized by each type of the antibody were selected...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345290/role-of-nestin-expression-in-angiogenesis-and-breast-cancer-progression
#12
Aleksandra Nowak, Jędrzej Grzegrzółka, Alicja Kmiecik, Aleksandra Piotrowska, Rafał Matkowski, Piotr Dzięgiel
Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345064/tlr8-ligation-induces-apoptosis-of-monocytic-myeloid-derived-suppressor-cells
#13
Yushe Dang, Zina J Rutnam, Gregory Dietsch, Hailing Lu, Yi Yang, Robert Hershberg, Mary L Disis
Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral blood of cancer patients and demonstrate cancer-promoting activity across multiple tumor types. A limited number of agents are known to impact MDSC activity. TLR8 is expressed in myeloid cells. We investigated expression of TLR8 on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and function. TLR8 was highly expressed in monocytic MDSC (mMDSC) but absent in granulocytic MDSC (gMDSC). Treatment of human PBMC with motolimod reduced the levels of mMDSC in volunteers and cancer donors versus control (P < 0...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344803/toxoplasma-gondii-prevalence-and-characterization-of-new-genotypes-in-free-range-chickens-from-south-brazil
#14
Fernando Emmanuel Gonçalves Vieira, João Pedro Sasse, Ana Flávia Minutti, Ana Carolina Miura, Luiz Daniel de Barros, Sergio Tosi Cardim, Thais Agostinho Martins, Mércia de Seixas, Milton Issashi Yamamura, Chunlei Su, João Luis Garcia
Toxoplasma gondii is an intracellular parasite that can infect all warm-blooded animals including humans. Recent studies showed that T. gondii strains from South America are genetically diverse. The present work aimed to determine T. gondii prevalence in free-ranging chicken in northwest Parana state in Brazil by two serological tests, to isolate the parasites from seropositive chickens and to genotype the isolates. Antibodies to T. gondii in 386 serum samples from 24 farms were investigated by immunofluorescence antibody assay (IFA) and modified agglutination test (MAT)...
January 18, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29344668/blocking-of-autocrine-igf-1-reduces-viability-of-human-umbilical-cord-mesenchymal-stem-cells-via-inhibition-of-the-akt-gsk-3%C3%AE-signaling-pathway
#15
Qi Wang, Fenxi Zhang, Yan Hong
Human umbilical cord mesenchymal stem cells (hUCMSCs) are able to secrete growth factors, such as hepatocyte growth factor, vascular endothelial growth factor and insulin‑like growth factor‑1 (IGF‑1). The secretion of these growth factors by transplanted hUCMSCs have been identified to stimulate the growth of the host cells in the target organs or tissues. The aim of the present study was to investigate the effect of autocrine IGF‑1 on cell viability of hUCMSCs. The expression levels of IGF‑1 and the IGF‑1 receptor (IGF‑1R) in hUCMSCs were identified using immunocytochemistry staining...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344586/systemic-multilineage-engraftment-in-mice-after-in-utero-transplantation-with-human-hematopoietic-stem-cells
#16
Russell G Witt, Emily M Kreger, Laura B Buckman, Patriss W Moradi, Phong T Ho, S Christopher Derderian, Perry Tsai, Chris Baker, Nathaniel Schramm, Rachel Cleary, J Victor Garcia, Tippi C MacKenzie
IUHCT of human cord blood-derived CD34+ cells into fetal NSG mice results in systemic multilineage engraftment with human cells.Preconditioning with in utero injection of an anti-c-Kit receptor antibody (ACK2) results in an improved rate of engraftment.
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29344330/developments-in-rare-bone-diseases-and-mineral-disorders
#17
REVIEW
Siobhan Bacon, Rachel Crowley
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29344327/secukinumab-a-review-of-the-anti-il-17a-biologic-for-the-treatment-of-psoriasis
#18
REVIEW
Jillian Frieder, Dario Kivelevitch, Alan Menter
Psoriasis is a systemic inflammatory disease associated with numerous comorbidities and a profound impact on patients' quality of life. While its complex immune pathogenesis is still not fully delineated, current evidence supports a fundamental role of the T-helper-17 (TH-17) pathway and its related interleukin-17 (IL-17) cytokine. Thus, new antipsoriatic therapies have been developed to block this key cytokine and its downstream effects. Secukinumab is a fully humanized, monoclonal anti-IL-17A antibody, and the first in its class to be approved by the US Food and Drug Administration for the treatment of moderate to severe plaque psoriasis...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29344192/tslp-promotes-angiogenesis-of-human-umbilical-vein-endothelial-cells-by-strengthening-the-crosstalk-between-cervical-cancer-cells-and-eosinophils
#19
Bing Zhang, Chun-Yan Wei, Kai-Kai Chang, Jia-Jun Yu, Wen-Jie Zhou, Hui-Li Yang, Jun Shao, Jin-Jin Yu, Ming-Qing Li, Feng Xie
Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343892/first-two-bilateral-hand-transplantations-in-india-part-4-immediate-post-operative-care-immunosuppression-protocol-and-monitoring
#20
Subramania Iyer, Mohit Sharma, P Kishore, Jimmy Mathew, R Janarthanan, Raghuveer Reddy, Abhijeet Wakure, Sundeep Vijayaraghavan, S M Chetan Mali, Visakh Varma, Ashish Chaudhari, Swapnil Dhake, Akshay Omkumar, George Kurian, Rajesh Nair, Anil Mathew, Zachariah Paul, Malini Eapen, Lalitha Biswas
Introduction: Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self ' from the 'non-self '. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'. Materials and Methods: Pre-operative evaluation of the recipient evaluation included immunological assessment in the form of panel reactive antibodies (PRA), human leucocyte antigen (HLA) typing, donor-specific antibody detection assays (DSA) and complement-dependent cytotoxicity assays (CDC)...
May 2017: Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India
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