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  1. Article ; Online: Acute leukaemia: no reason to panic.

    Ladikou, Eleni E / Ashworth, Iona / Seviar, Dale / Chevassut, Timothy

    Clinical medicine (London, England)

    2022  Volume 22, Issue 3, Page(s) 221–224

    Abstract: Acute leukaemia is characterised by uncontrolled expansion of immature leukocytes, either myeloid or lymphoid progenitors, leading to acute myeloid leukaemia (AML) and acute lymphoid leukaemia (ALL), respectively. If left untreated, it is life- ... ...

    Abstract Acute leukaemia is characterised by uncontrolled expansion of immature leukocytes, either myeloid or lymphoid progenitors, leading to acute myeloid leukaemia (AML) and acute lymphoid leukaemia (ALL), respectively. If left untreated, it is life-threatening and can lead to death within weeks. When acute leukaemia is suspected, urgent haematology input should be sought. Appropriate investigations are needed promptly to confirm diagnosis and start treatment. A multidisciplinary approach is vital to ensure appropriate management.
    MeSH term(s) Acute Disease ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/therapy
    Language English
    Publishing date 2022-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.2022-0149
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5439: Show issues Location:
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  2. Article ; Online: COVID-19 mortality in patients on anticoagulants and antiplatelet agents.

    Sivaloganathan, Helena / Ladikou, Eleni E / Chevassut, Timothy

    British journal of haematology

    2020  Volume 190, Issue 4, Page(s) e192–e195

    MeSH term(s) Aged ; Aged, 80 and over ; Anticoagulants/administration & dosage ; COVID-19/blood ; COVID-19/drug therapy ; COVID-19/mortality ; Disease-Free Survival ; Female ; Hospital Mortality ; Humans ; Male ; Platelet Aggregation Inhibitors/administration & dosage ; SARS-CoV-2 ; Survival Rate
    Chemical Substances Anticoagulants ; Platelet Aggregation Inhibitors
    Keywords covid19
    Language English
    Publishing date 2020-07-19
    Publishing country England
    Document type Comparative Study ; Letter ; Randomized Controlled Trial
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.16968
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Lymphocytosis and chronic lymphocytic leukaemia: investigation and management.

    Devi, Amarpreet / Thielemans, Lieze / Ladikou, Eleni E / Nandra, Taran K / Chevassut, Timothy

    Clinical medicine (London, England)

    2022  Volume 22, Issue 3, Page(s) 225–229

    Abstract: Lymphocytosis is a common blood-test finding. Establishing whether the cause of lymphocytosis is benign or malignant is key to managing patients appropriately. A lymphocytosis should always prompt clinical review including a thorough history, examination ...

    Abstract Lymphocytosis is a common blood-test finding. Establishing whether the cause of lymphocytosis is benign or malignant is key to managing patients appropriately. A lymphocytosis should always prompt clinical review including a thorough history, examination and appropriate preliminary investigations (blood tests, blood film). The majority of patients with chronic lymphocytic leukaemia (CLL) present incidentally due to a lymphocytosis found on routine blood tests. Patient outcomes vary considerably based on genetic pre-disposition and various prognostic markers (age, Binet or Rai staging, and B2-microglobulin). Although not curative, chemo-immunotherapy is an effective treatment strategy for the majority of CLL patients with progressive disease. More recently, novel oral therapies have been developed that target key signalling and apoptosis pathways and that are being used in relapse settings and as first-line treatments for certain patients.
    MeSH term(s) Humans ; Immunotherapy ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Lymphocytosis/drug therapy ; Lymphocytosis/therapy ; Neoplasm Recurrence, Local ; Prognosis ; Treatment Outcome
    Language English
    Publishing date 2022-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.2022-0150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  5. Article ; Online: COVID‐19 mortality in patients on anticoagulants and antiplatelet agents

    Sivaloganathan, Helena / Ladikou, Eleni E / Chevassut, Timothy

    British Journal of Haematology

    2020  Volume 190, Issue 4

    Keywords Hematology ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.16968
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    In stock of ZB MED Cologne/Königswinter

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  6. Article ; Online: Dissecting the role of the CXCL12/CXCR4 axis in acute myeloid leukaemia.

    Ladikou, Eleni E / Chevassut, Timothy / Pepper, Chris J / Pepper, Andrea Gs

    British journal of haematology

    2020  Volume 189, Issue 5, Page(s) 815–825

    Abstract: Acute myeloid leukaemia (AML) is the most common adult acute leukaemia with the lowest survival rate. It is characterised by a build-up of immature myeloid cells anchored in the protective niche of the bone marrow (BM) microenvironment. The CXCL12/CXCR4 ... ...

    Abstract Acute myeloid leukaemia (AML) is the most common adult acute leukaemia with the lowest survival rate. It is characterised by a build-up of immature myeloid cells anchored in the protective niche of the bone marrow (BM) microenvironment. The CXCL12/CXCR4 axis is central to the pathogenesis of AML as it has fundamental control over AML cell adhesion into the protective BM niche, adaptation to the hypoxic environment, cellular migration and survival. High levels of CXCR4 expression are associated with poor relapse-free and overall survival. The CXCR4 ligand, CXCL12 (SDF-1), is expressed by multiple cells types in the BM, facilitating the adhesion and survival of the malignant clone. Blocking the CXCL12/CXCR4 axis is an attractive therapeutic strategy providing a 'multi-hit' therapy that both prevents essential survival signals and releases the AML cells from the BM into the circulation. Once out of the protective niche of the BM they would be more susceptible to destruction by conventional chemotherapeutic drugs. In this review, we disentangle the diverse roles of the CXCL12/CXCR4 axis in AML. We then describe multiple CXCR4 inhibitors, including small molecules, peptides, or monoclonal antibodies, which have been developed to date and their progress in pre-clinical and clinical trials. Finally, the review leads us to the conclusion that there is a need for further investigation into the development of a 'multi-hit' therapy that targets several signalling pathways related to AML cell adhesion and maintenance in the BM.
    MeSH term(s) Animals ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/blood ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Bone Marrow/pathology ; Cell Adhesion/drug effects ; Cell Adhesion/physiology ; Cell Hypoxia ; Cell Movement/physiology ; Cell-Derived Microparticles ; Chemokine CXCL12/physiology ; Clinical Trials as Topic ; Drug Evaluation, Preclinical ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Leukemic/drug effects ; Gene Expression Regulation, Leukemic/physiology ; Heterocyclic Compounds/pharmacology ; Heterocyclic Compounds/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/blood ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/metabolism ; Leukemia, Myeloid, Acute/pathology ; Mice ; Molecular Targeted Therapy ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/physiology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Peptides/therapeutic use ; Peptides, Cyclic/therapeutic use ; Pyridines/therapeutic use ; Receptors, CXCR4/antagonists & inhibitors ; Receptors, CXCR4/physiology ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Stem Cell Niche ; Stromal Cells/metabolism ; Stromal Cells/pathology ; Tumor Microenvironment
    Chemical Substances 4-fluorobenzoyl-TN-14003 ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; CXCL12 protein, human ; CXCR4 protein, human ; CXCR4 protein, mouse ; Chemokine CXCL12 ; Heterocyclic Compounds ; LY2510924 ; N-(1,4,8,11- tetraazacyclotetradecanyl-1,4-phenylenebis(methylene))-2-(aminomethyl)- pyridine ; Neoplasm Proteins ; Peptides ; Peptides, Cyclic ; Pyridines ; Receptors, CXCR4 ; ulocuplumab (7KNP87L4X4) ; plerixafor (S915P5499N)
    Language English
    Publishing date 2020-03-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.16456
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.182: Show issues Location:
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  7. Article ; Online: COVID-19 mortality in patients on anticoagulants and antiplatelet agents

    Sivaloganathan, Helena / Ladikou, Eleni E / Chevassut, Timothy

    2020  

    Abstract: Coagulopathy (Tang, et al 2020) and a prothrombotic diathesis with high D-dimer and fibrinogen levels (Al-Samkari, et al 2020) are associated with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ...

    Abstract Coagulopathy (Tang, et al 2020) and a prothrombotic diathesis with high D-dimer and fibrinogen levels (Al-Samkari, et al 2020) are associated with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Extensive thrombosis in small vessels and the microvasculature in lungs and extrapulmonary organs has been confirmed histologically (Zhang, et al 2020). Early studies showed that the venous thromboembolism (VTE) incidence in hospitalised COVID-19 patients can be as high as 25% (Songping, et al 2020), and more recent studies have indicated this can be expanded to other macrovascular thrombotic complications, such as a higher than expected prevalence of pulmonary emboli in patients with COVID-19 (Klok, et al 2020, Stoneham, et al). The term “diffuse pulmonary intravascular coagulopathy” has been proposed to describe the lung-restricted vascular immunopathology associated with COVID-19. This is distinct from disseminated intravascular coagulation in its early stages and is characterised by increased D-dimer with normal platelet count and normal/elevated fibrinogen (McGonagle, et al 2020). Increased VTE rate has been associated with higher D-dimer level, and in the same study, an association between VTE and death was found (Middeldorp, et al 2020). Another study has shown a D-dimer greater than 1 μg/mL was associated with a poorer prognosis (Zhou, et al 2020). Patients requiring mechanical ventilation who were treated with therapeutic anticoagulation had an in-hospital mortality of 29.1% compared to 62.7% in patients who did not receive anticoagulation. Longer duration of anticoagulation was associated with a reduced risk of mortality (Paranjpe, et al 2020).
    Keywords R Medicine ; RB Pathology ; RM Therapeutics. Pharmacology ; covid19
    Subject code 610
    Language English
    Publishing date 2020-06-25
    Publisher Wiley
    Publishing country uk
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Elucidation of Focal Adhesion Kinase as a Modulator of Migration and Invasion and as a Potential Therapeutic Target in Chronic Lymphocytic Leukemia.

    Burley, Thomas A / Hesketh, Andrew / Bucca, Giselda / Kennedy, Emma / Ladikou, Eleni E / Towler, Benjamin P / Mitchell, Simon / Smith, Colin P / Fegan, Christopher / Johnston, Rosalynd / Pepper, Andrea / Pepper, Chris

    Cancers

    2022  Volume 14, Issue 7

    Abstract: The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance, leading to subsequent disease relapse. The aim of this study was to ... ...

    Abstract The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance, leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier, and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype, and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model, we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with an overrepresentation of adhesion and cell migration gene sets. From this analysis, an upregulation of the FAK signaling pathway was observed. Importantly,
    Language English
    Publishing date 2022-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14071600
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The emerging role of estrogen in B cell malignancies.

    Ladikou, Eleni-Eirini / Kassi, Eva

    Leukemia & lymphoma

    2016  Volume 58, Issue 3, Page(s) 528–539

    Abstract: Increasing evidence implicates a role of estrogens in hematological malignancies. We reviewed current knowledge on the emerging role of estrogens and estrogen receptors in normal B-cell function, chronic lymphocytic leukemia, and B-cell lymphoma. Data ... ...

    Abstract Increasing evidence implicates a role of estrogens in hematological malignancies. We reviewed current knowledge on the emerging role of estrogens and estrogen receptors in normal B-cell function, chronic lymphocytic leukemia, and B-cell lymphoma. Data support that (1) normal human peripheral blood cells (mononuclear cells, total lymphocytes, T as well as B lymphocytes, and NK cells) express both estrogen receptor subtypes (ERα and ERβ), (2) B-cell malignancies express mainly ERβ while selective ERβ agonists inhibit cell growth and induce apoptosis, (3) estrogens regulate, via an ER-mediated pathway, gene expression of cyclins, kinases, bcl-2 proto-oncogene, activation-induced deaminase (AID), and transcription factors, associated with changes in BCR signaling and B cell tumorigenesis. In conclusion, estrogen receptors play an important role in normal B-cell function and B-cell tumorigenesis; however, further investigations are required to delineate the role of estrogens and estrogen receptors in the etiopathogenesis and therapy of B-cell malignancies.
    MeSH term(s) Animals ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Epigenesis, Genetic ; Estrogens/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, B-Cell/etiology ; Leukemia, B-Cell/metabolism ; Leukemia, B-Cell/mortality ; Leukemia, B-Cell/pathology ; Lymphoma, B-Cell/etiology ; Lymphoma, B-Cell/metabolism ; Lymphoma, B-Cell/mortality ; Lymphoma, B-Cell/pathology ; Mitochondria/genetics ; Mitochondria/metabolism ; Prognosis ; Receptors, Estrogen/metabolism ; Signal Transduction
    Chemical Substances Estrogens ; Receptors, Estrogen
    Language English
    Publishing date 2016-08-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2016.1213828
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2997: Show issues Location:
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  10. Article: Targeting the Non-Canonical NF-κB Pathway in Chronic Lymphocytic Leukemia and Multiple Myeloma.

    Burley, Thomas A / Kennedy, Emma / Broad, Georgia / Boyd, Melanie / Li, David / Woo, Timothy / West, Christopher / Ladikou, Eleni E / Ashworth, Iona / Fegan, Christopher / Johnston, Rosalynd / Mitchell, Simon / Mackay, Simon P / Pepper, Andrea G S / Pepper, Chris

    Cancers

    2022  Volume 14, Issue 6

    Abstract: In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B- and T-lymphocytes. Basal NF-κB subunit activity was characterized ... ...

    Abstract In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B- and T-lymphocytes. Basal NF-κB subunit activity was characterized using an enzyme linked immunosorbent assay (ELISA), and the effects of NIK inhibition were then assessed in terms of cytotoxicity and the expression of nuclear NF-κB subunits following monoculture and co-culture with CD40L-expressing fibroblasts, as a model of the lymphoid niche. CW15337 induced a dose-dependent increase in apoptosis, and nuclear expression of the non-canonical NF-κB subunit, p52, was correlated with sensitivity to CW15337 (
    Language English
    Publishing date 2022-03-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14061489
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