Search results for "SCID"
showing 10 items of 252 documents
T cells engineered to express a T-cell receptor specific for glypican-3 to recognize and kill hepatoma cells in vitro and in mice
2015
Background & Aims Cancer therapies are being developed based on our ability to direct T cells against tumor antigens. Glypican-3 (GPC3) is expressed by 75% of all hepatocellular carcinomas (HCC), but not in healthy liver tissue or other organs. We aimed to generate T cells with GPC3-specific receptors that recognize HCC and used them to eliminate GPC3-expressing xenograft tumors grown from human HCC cells in mice. Methods We used mass spectrometry to obtain a comprehensive peptidome from GPC3-expressing hepatoma cells after immune-affinity purification of human leukocyte antigen (HLA)-A2 and bioinformatics to identify immunodominant peptides. To circumvent GPC3 tolerance resulting from feta…
Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia
2021
BackgroundT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients.MethodsUMG1 expression was assessed by immunohistochemistry (IHC) on a wide panel of normal t…
Human NK cells selective targeting of colon cancer-initiating cells: a role for natural cytotoxicity receptors and MHC class I molecules
2013
Abstract Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the “differentiated” cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly p…
Proboscidea: a preliminary note
1990
Abstract Proboscidean remains collected during the 1983–1989 field seasons are described here. They are assigned to Deinotherium aff. levius (14 isolated teeth) and to Gomphotherium pasalarense (44 isolated teeth). No evidence was found for another subspecies described by Gaziry from Pasalar. The proboscidea are probably indicative of woodland conditions at Pasalar.
Conformation constraints for efficient viscoelastic fluid simulation
2017
The simulation of high viscoelasticity poses important computational challenges. One is the difficulty to robustly measure strain and its derivatives in a medium without permanent structure. Another is the high stiffness of the governing differential equations. Solutions that tackle these challenges exist, but they are computationally slow. We propose a constraint-based model of viscoelasticity that enables efficient simulation of highly viscous and viscoelastic phenomena. Our model reformulates, in a constraint-based fashion, a constitutive model of viscoelasticity for polymeric fluids, which defines simple governing equations for a conformation tensor. The model can represent a diverse pa…
Tributyltin chloride-induced effects on protein tyrosine phosphorylation and on extracellular-signal-regulated kinase (ERK) phosphorilation in Ascidi…
2011
Ascidians represent an intriguing candidate experimental system for studying the effects of environmental stress. We studied TBT effects and probable related pathways were investigated on ascidian embryos by using Western immunoblotting. Among the various signal transduction pathways involved in response to environmental stress, both tyrosine kinase signalling and MAPKs have been played a significant role. To better understand molecular mechanisms after exposure to TBT we studied the two signal transduction pathways above mentioned. Attempting to unravel the molecular effects of TBT-induced on ascidians embryogenesis, TBT treatments carried out in Phallusia mammillata embryos at gastrula st…
Effects of tributyltin chloride in ascidian embryos: modulation of kinase-mediated signalling pathways
2009
We studied the effects of various TBT concentrations by assaying the activity of ERK 1/2 (p44/42) and phospho-ERK1/2 (phospho-p44/42), proteins with a key role in ascidian development, and tyrosine kinase-dependent pathway. The effects of this xenobiotic and the role of some signalling mechanisms on ascidian embryos were examined by using Western immunoblotting. The tyrosine phosphorylation pattern in the ascidians Ciona intestinalis and Phallusia mammillata development was examined and different levels of protein phosphorylation were found as a response to TBT at μM range. To determine whether another key signalling pathway was activated, the effects of TBT on the phosphorylation state of …
How initial and boundary conditions affect protoplanetary migration in a turbulent sub-Keplerian accretion disc: 2D non-viscous SPH simulations
2009
Current theories on planetary formation establish that giant planet formation should be contextual to their quick migration towards the central star due to the protoplanets-disc interactions on a timescale of the order of $10^5$ years, for objects of nearly 10 terrestrial masses. Such a timescale should be smaller by an order of magnitude than that of gas accretion onto the protoplanet during the hierarchical growing-up of protoplanets by collisions with other minor objects. These arguments have recently been analysed using N-body and/or fluid-dynamics codes or a mixing of them. In this work, inviscid 2D simulations are performed, using the SPH method, to study the migration of one protopla…
Tardigrades of Finland: new records and an annotated checklist
2020
Species checklists are powerful and important tools of communication between taxonomists and applied environmental biologists, which in turn lead to well-planned and successful conservation strategies and ecological studies. Despite this, only recently the interest on compiling systematic checklists is growing among taxonomists who study tardigrades—micrometazoans that inhabit almost every habitat worldwide. As the Finnish records of tardigrades (a.k.a. water bears) species are incomplete, outdated and no checklist has ever been compiled for this country, an easy-to-consult checklist is here reported. This checklist covers all Finnish tardigrade taxa identified in the past and in the 13 sam…
Overexpression of the truncated form of high mobility group a proteins (HMGA2) in human myometrial cells induces leiomyoma-like tissue formation
2014
The pathogenesis of uterine leiomyomas, the most common benign tumor in women, is still unknown. This lack of basic knowledge limits the development of novel non-invasive therapies. Our group has previously demonstrated that leiomyoma side population (SP) cells are present in tumor lesions and act like putative tumor-initiating stemcells in human leiomyoma. Moreover, accumulated evidence demonstrates that these benign tumors of mesenchymal origin are characterized by rearrangements of the High Mobility Group A proteins (HMGA). In this work, we tested the hypothesis that leiomyoma development may be due to overexpression of HMGA2 (encoding high mobility group AT-hook2) in myometrial stem cel…