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  • 1
    Language: English
    In: Leukemia, 2017-01, Vol.31 (1), p.18-25
    Description: Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, 〈0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P〈0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P〈0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.
    Subject(s): fms-Like Tyrosine Kinase 3 - genetics ; Disease-Free Survival ; Leukemia, Myeloid, Acute - diagnosis ; Prognosis ; Epigenesis, Genetic - genetics ; Humans ; Child, Preschool ; Retrospective Studies ; Gene Expression Regulation, Leukemic ; Child ; Neoplasm, Residual - genetics ; Leukemia, Myeloid, Acute - genetics ; Molecular targeted therapy ; Gene mutations ; Gene expression ; Health aspects ; Innovations ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Ultramicroscopy, 2003, Vol.94 (2), p.89-98
    Description: Experimental and theoretical results on image contrast of semiconductor multi-layers in scanning electron microscopy investigation are reported. Two imaging modes have been considered: backscattered electron imaging of bulk specimen and scanning transmission imaging of thinned specimens. The following main results have been reached. The image resolution of the multi-layers is, in both cases, defined by the probe size. The contrast, governed by density and atomic number differences, is affected by the size of the interaction volume in backscattered electron imaging and by the beam broadening in scanning transmission. Operating in the scanning transmission mode, the contrast of bright field images can be easily related to local variation in atomic number and density of the specimen while the dark field image contrast is strongly affected by electron beam energy, detector collection angles and specimen thickness. All these factors are able to produce contrast reversals that are difficult to explain without the support of a suitable simulation code.
    Subject(s): Scanning transmission electron microscopy ; Scanning electron microscopy ; Backscattered electrons imaging ; Electron, positron and ion microscopes, electron diffractometers and related techniques ; Electron, ion, and scanning probe microscopy ; Electron, positron, and ion microscopes, electron diffractometers, and related techniques ; Transmission, reflection and scanning electron microscopy(including ebic) ; Exact sciences and technology ; Condensed matter: structure, mechanical and thermal properties ; Instruments, apparatus, components and techniques common to several branches of physics and astronomy ; General ; Structure of solids and liquids; crystallography ; Physics
    ISSN: 0304-3991
    E-ISSN: 1879-2723
    Source: Backfile Package - All of Back Files EBS [ALLOFBCKF]
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2008-06, Vol.41 (S2), p.S3-S7
    Description: Over the past decade, relevant improvements and refinements have significantly changed the indications, technique and results obtained with allogeneic hematopoietic SCT (HSCT) in childhood. A fundamental turning point in the history of allogeneic HSCT is represented by the use of placental blood, which was first employed in 1988 in a patient with Fanconi anemia, successfully transplanted with cord blood cells from an HLA-identical sibling. Since then, thousands of children were given an allograft of cord blood-derived hematopoietic progenitors, mainly from an unrelated donor. This large clinical experience has documented that, as compared with BMT, cord blood transplantation (CBT) is associated with reduced incidence and severity of GvHD. The outcome of recipients given unrelated CBT has been reported to be at least as good as that of patients transplanted with either BM or peripheral blood mobilized cells of an unrelated volunteer. Another emerging strategy of HSCT is that of using HLA-partially matched relatives as donors of hematopoietic progenitors. The infusion of a huge number of positively in vitro-selected CD34+ cells, with the concomitant removal of T cells, has been demonstrated to permit sustained engraftment of donor hematopoiesis, without the occurrence of GvHD in the majority of patients transplanted from an HLA-disparate relative. In adults given this type of transplantation, the most favorable results have been reported for AMLs and when the donor displays alloreactivity of natural killer cells. It remains to be definitively proved whether these findings documented in adults maintain their value in pediatric patients transplanted from an HLA-disparate family donor. Finally, the last few years have witnessed the emergence of approaches of adoptive cell therapy aimed at optimizing the results of allograft through strategies able to reinforce immune competence against pathogens, as well as against tumor cells, or at modulating donor T-cell alloreactivity.
    Subject(s): Immunotherapy, Adoptive ; Humans ; Bone Marrow Transplantation - adverse effects ; Hematopoietic Stem Cell Transplantation ; Graft Survival ; Child ; Mesenchymal Stem Cell Transplantation ; Transplantation, Homologous ; Cord Blood Stem Cell Transplantation ; Fetal blood ; Complications and side effects ; Usage ; Transplantation ; Histocompatibility testing ; Methods ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
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  • 4
    Language: English
    In: Journal of Cancer, 2011, Vol.2 (1), p.341-346
    Description: Among the novel biologic therapeutics that will increase our ability to cure human cancer in the years to come, T cell therapy is one of the most promising approaches. However, with the possible exception of tumor-infiltrating lymphocytes therapy for melanoma, clinical trials of adoptive T-cell therapy for solid tumors have so far provided only clear proofs-of-principle to build on with further development. Epstein-Barr virus (EBV)-associated malignancies offer a unique model to develop T cell-based immune therapies, targeting viral antigens expressed on tumor cells. In the last two decades, EBV-specific cytotoxic T-lymphocytes (CTL) have been successfully employed for the prophylaxis and treatment of EBV-related lymphoproliferative disorders in immunocompromised hosts. More recently, this therapeutic approach has been applied to the setting of EBV-related solid tumors, such as nasopharyngeal carcinoma. The results are encouraging, although further improvements to the clinical protocols are clearly necessary to increase anti-tumor activity. Promising implementations are underway, including harnessing the therapeutic potential of CTLs specific for subdominant EBV latent cycle epitopes, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells.
    ISSN: 1837-9664
    E-ISSN: 1837-9664
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Applied physics letters, 2005-03-04, Vol.86 (10), p.101916-101916-3
    Description: We show that, in scanning electron microscopy, it is possible to use the secondary electrons produced by the backscattered electrons to obtain chemical information on the dopant distribution in Sb-implanted silicon. Theoretical investigations and experimental data concur to point out that the resolution of the method is defined by the probe size-values of 1 nm or even lower are possible in the present instruments-while the contrast depends on the electron range and on the boundary conditions. A proper choice of beam energy and boundaries of the doped layer may allow a sensitivity below 1%, suitable to characterize the high-dose near-surface region of the ultrashallow junctions in cross-sectioned bulk specimens.
    ISSN: 0003-6951
    E-ISSN: 1077-3118
    Source: American Institute of Physics (AIP) Publications
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  • 6
    Article
    Article
    2004
    ISSN: 0304-3991 
    Language: English
    In: Ultramicroscopy, 2004, Vol.99 (2), p.201-209
    Description: The calibration of a modern electron microscope for Lorentz microscopy observations has been performed using diffractogram, Fresnel diffraction fringe analysis and low-angle electron diffraction methods. An example related to the observations of electrostatic fields associated to a thinned reverse-biased p–n junction is also reported.
    Subject(s): Lorentz microscopy ; Calibration ; p–n junctions ; Electron microscopy
    ISSN: 0304-3991
    E-ISSN: 1879-2723
    Source: Backfile Package - All of Back Files EBS [ALLOFBCKF]
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Journal of microscopy (Oxford), 2005-05, Vol.218 (2), p.180-184
    Description: Summary We consider the effects of different boundaries on the visibility of a specimen detail providing a compositional contrast in scanning electron microscopy, operating with backscattered electrons or secondary electrons. An object characterized by a gradual variation in composition, an As‐doped region in Si, is investigated. The different boundaries in the cross‐sectioned specimen correspond to the absence or presence of a poly‐Si layer on top of the implanted region, deposited after the annealing treatment. It is shown that the interpretation model used for image formation is of paramount relevance for understanding the experimental results, indicating that the boundaries of the doped region are important in hindering or enhancing its visibility. The relevance of experimental parameters such as electron energy and probe dimension is also reported.
    Subject(s): dopant profiling ; scanning electron microscpy ; secondary electrons ; Backsattered electrons imaging ; boundary conditions
    ISSN: 0022-2720
    E-ISSN: 1365-2818
    Source: Academic Search Ultimate
    Source: Wiley Online Library All Backfiles
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Oncoimmunology, 2017-02-01, Vol.6 (2), p.e1216291-e1216291
    Description: We demonstrated that γδ T cells of patients given HLA-haploidentical HSCT after removal of αβ + T cells and CD19 + B cells are endowed with the capacity of killing leukemia cells after ex vivo treatment with zoledronic acid (ZOL). Thus, we tested the hypothesis that infusion of ZOL in patients receiving this type of graft may enhance γδ T-cell cytotoxic activity against leukemia cells. ZOL was infused every 28 d in 43 patients; most were treated at least twice. γδ T cells before and after ZOL treatments were studied in 33 of these 43 patients, till at least 7 mo after HSCT by high-resolution mass spectrometry, flow-cytometry, and degranulation assay. An induction of Vδ2-cell differentiation, paralleled by increased cytotoxicity of both Vδ1 and Vδ2 cells against primary leukemia blasts was associated with ZOL treatment. Cytotoxic activity was further increased in Vδ2 cells, but not in Vδ1 lymphocytes in those patients given more than one treatment. Proteomic analysis of γδ T cells purified from patients showed upregulation of proteins involved in activation processes and immune response, paralleled by downregulation of proteins involved in proliferation. Moreover, a proteomic signature was identified for each ZOL treatment. Patients given three or more ZOL infusions had a better probability of survival in comparison to those given one or two treatments (86% vs. 54%, respectively, p = 0.008). Our data indicate that ZOL infusion in pediatric recipients of αβ T- and B-cell-depleted HLA-haploidentical HSCT promotes γδ T-cell differentiation and cytotoxicity and may influence the outcome of patients.
    Subject(s): γδ T cells ; proteomic ; leukemic patients ; haematopoietic stem cell transplantation ; zoledronic acid ; γδ t cells
    ISSN: 2162-4011
    ISSN: 2162-402X
    E-ISSN: 2162-402X
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Article
    Article
    2005
    ISSN: 1431-9276 
    Language: English
    In: Microscopy and microanalysis, 2005-02, Vol.11 (1), p.97-104
    Description: A conventional scanning electron microscope equipped with a LaB6 source has been modified to operate in a scanning transmission mode. Two detection strategies have been considered, one based on the direct collection of transmitted electrons, the other on the collection of secondary electrons resulting from the conversion of the transmitted ones. Two types of specimens have been mainly investigated: semiconductor multilayers and dopant profiles in As-implanted Si. The results show that the contrast obeys the rules of mass–thickness contrast whereas the resolution is always defined by the probe size independently of specimen thickness and beam broadening. The detection strategy may affect the bright field (light regions look brighter) or dark field (heavy regions look brighter) appearance of the image. Using a direct collection of the transmitted electrons, the contrast can be deduced from the angular distribution of transmitted electrons and their collection angles. When collecting the secondary electrons to explain the image contrast, it is also necessary to take into account the secondary yield dependence on the incidence angle of the transmitted electrons.
    Subject(s): INSTRUMENTATION AND TECHNIQUES
    ISSN: 1431-9276
    E-ISSN: 1435-8115
    Source: Hellenic Academic Libraries Link
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Physical review. B, Condensed matter and materials physics, 2005, Vol.72 (8), p.085312.1-085312.5
    Subject(s): Surfaces and interfaces; thin films and whiskers (structure and nonelectronic properties) ; Solid surfaces and solid-solid interfaces ; Physics ; Exact sciences and technology ; Condensed matter: structure, mechanical and thermal properties
    ISSN: 1098-0121
    E-ISSN: 1550-235X
    Source: Single Journals
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