Search results for "Raf"
showing 10 items of 11050 documents
Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the onc…
2015
abstract The fetal tight junction molecule claudin 6 (CLDN6) is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need. We engineered 6PHU3, a T-cell-engaging bispecific single chain molecule (bi-(scFv)2) with anti-CD3/anti-CLDN6 specificities, and characterized its pharmacodynamic properties. Our data show that upon engagement by 6PHU3, T cells strongly upregulate cytotoxicity and activation markers, proliferate and acquire an effector phenotype. 6PHU3 exerts potent killing of cancer cells in vitro with EC50 values in the pg/mL range. Subcutaneous xenograft tumors in NSG mice engrafted with human PBMCs are eradicat…
Humanized mice in cutaneous leishmaniasis—Suitability analysis of human PBMC transfer into immunodeficient mice
2019
Humanized mice represent a suitable preclinical test system for example therapeutic interventions in various disease settings, including infections. Here, we intended to establish such system for cutaneous leishmaniasis by infecting T, B and NK cell-deficient mice adoptively transferred with human peripheral blood mononuclear cells (PBMC). L major infection led to the establishment of parasite lesions harbouring viable parasites and human T cells, but parasite elimination was not seen due to a species-specific activity of T cell-derived human IFNγ. In addition, up to 50% of infected mice succumbed to severe graft-versus-host disease. In summary, even though long-term disease outcome assessm…
Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma.
2018
Abstract The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors derived from seven patients with melanoma and characterize their interactions with their tumor-infiltrating lymphocytes (TIL). Our investigation of the antigenic and T-cell landscapes encompassing the TAA and neoantigen signatures, their immune reactivity, and their corresponding T-cell identities provides the first comprehensive analysis of cancer cell T-cell cosignatures, allowing us to discover remarkable antigenic and TIL similarities b…
Summertime observations of ultrafine particles and cloud condensation nuclei from the boundary layer to the free troposphere in the Arctic
2016
Abstract. The Arctic is extremely sensitive to climate change. Shrinking sea ice extent increases the area covered by open ocean during Arctic summer, which impacts the surface albedo and aerosol and cloud properties among many things. In this context extensive aerosol measurements (aerosol composition, particle number and size, cloud condensation nuclei, and trace gases) were made during 11 flights of the NETCARE July, 2014 airborne campaign conducted from Resolute Bay, Nunavut (74N, 94W). Flights routinely included vertical profiles from about 60 to 3000 m a.g.l. as well as several low-level horizontal transects over open ocean, fast ice, melt ponds, and polynyas. Here we discuss the vert…
Evolutionary conserved mechanisms pervade structure and transcriptional modulation of allograft inflammatory factor-1 from sea anemone Anemonia virid…
2017
Gene family encoding allograft inflammatory factor-1 (AIF-1) is well conserved among organisms; however, there is limited knowledge in lower organisms. In this study, the first AIF-1 homologue from cnidarians was identified and characterised in the sea anemone Anemonia viridis. The full-length cDNA of AvAIF-1 was of 913 bp with a 5' -untranslated region (UTR) of 148 bp, a 3'-UTR of 315 and an open reading frame (ORF) of 450 bp encoding a polypeptide with149 amino acid residues and predicted molecular weight of about 17 kDa. The predicted protein possesses evolutionary conserved EF hand Ca2+ binding motifs, post-transcriptional modification sites and a 3D structure which can be superimposed …
Actin Filaments Are Involved in the Coupling of V0-V1 Domains of Vacuolar H+-ATPase at the Golgi Complex*
2016
We previously reported that actin-depolymerizing agents promote the alkalization of the Golgi stack and the trans-Golgi network. The main determinant of acidic pH at the Golgi is the vacuolar-type H+-translocating ATPase (V-ATPase), whose V1 domain subunits B and C bind actin. We have generated a GFP-tagged subunit B2 construct (GFP-B2) that is incorporated into the V1 domain, which in turn is coupled to the V0 sector. GFP-B2 subunit is enriched at distal Golgi compartments in HeLa cells. Subcellular fractionation, immunoprecipitation, and inversal FRAP experiments show that the actin depolymerization promotes the dissociation of V1-V0 domains, which entails subunit B2 translocation from Go…
Seasonal and spatial dynamics of enteric viruses in wastewater and in riverine and estuarine receiving waters
2018
International audience; Enteric viruses represent a global public health threat and are implicated in numerous foodborne andwaterborne disease outbreaks. Nonetheless, relatively little is known of their fate and stability in the environment. In this studywe used carefully validatedmethods tomonitor enteric viruses, namely adenovirus (AdV), JC polyomavirus (JCV), noroviruses (NoVs), sapovirus (SaV) and hepatitis A and E viruses (HAV and HEV) fromwastewater source to beaches and shellfish beds. Wastewater influent and effluent, surface water, sediment and shellfish samples were collected in the Conwy catchment (North Wales, UK) once a month for one year. High concentrations of AdV and JCV wer…
Dextran production by Lactobacillus sakei MN1 coincides with reduced autoagglutination, biofilm formation and epithelial cell adhesion
2017
40 p.-7 fig.-4 fig.supl.
Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model
2019
Objective To study the effects of short- and long-term vitamin D treatment on uterine leiomyomas in vivo through cell proliferation, extracellular matrix (ECM) degradation, and apoptosis. Design Preclinical study of human leiomyoma treatment with vitamin D in an nonhuman animal model. Setting Hospital and university laboratories. Patient(s)/Animal(s) Human leiomyomas were collected from patients and implanted in ovariectomized NOD-SCID mice. Intervention(s) Mice were treated with vitamin D (0.5 μg/kg/d or 1 μg/kg/d) or vehicle for 21 or 60 days. Main Outcome Measure(s) Vitamin D effect in xenograft tissue was assessed by monitoring tumor size (18F-FDG positron-emission tomography/computeriz…
The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development.
2016
IF 7.932; International audience; Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitro to inhibit T-cell activation and to modulate endoplasmic reticulum (ER) stress to which intestinal cells are highly susceptible. Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, we explored here its ability to control intestinal acute GvHD in vivo in two mouse GvHD models (C57BL/6 -> BALB/c and FVB/N -> Lgr5-eGFP), ex vivo in intestine organoids and in vitro in …