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  1. Article ; Online: Multicancer Early Detection Tests: An Overview of Early Results From Prospective Clinical Studies and Opportunities for Oncologists.

    Post, Carl / Braun, Theodore P / Etzioni, Ruth / Nabavizadeh, Nima

    JCO oncology practice

    2023  Volume 19, Issue 12, Page(s) 1111–1115

    Abstract: A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ ... ...

    Abstract A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ screening paradigms. Pathways for clinical implementation of these novel MCED tests have not been delineated, particularly for the patients with signal positive results requiring additional confirmatory testing. In this overview, we highlight early results from prospective clinical studies testing the efficacy of genomic MCED tests in cohorts of patients without known cancer diagnoses. Additionally, we discuss a proposed professional expansion of the oncology practice relating to the diagnostic workup of individuals found to have an MCED signal positive for cancer. As MCED blood tests have the potential to dramatically upend current cancer screening paradigms and downstream cancer therapy, it is imperative for oncologists to be aware of important clinical studies and the multitude of unanswered questions. The current gaps in the clinical implication of these tests may serve as a meaningful and rewarding expansion of oncology practice.
    MeSH term(s) Humans ; Prospective Studies ; Neoplasms/diagnosis ; Neoplasms/genetics ; Medical Oncology ; Early Detection of Cancer ; Oncologists
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 3028198-2
    ISSN 2688-1535 ; 2688-1527
    ISSN (online) 2688-1535
    ISSN 2688-1527
    DOI 10.1200/OP.23.00260
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia: Updates From the LAST Study on Patient-Reported Outcomes and Biomarkers for Relapse.

    Braun, Theodore P / Druker, Brian J

    JAMA oncology

    2020  Volume 7, Issue 1, Page(s) 50–51

    MeSH term(s) Biomarkers ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Patient Reported Outcome Measures ; Protein Kinase Inhibitors/adverse effects ; Recurrence
    Chemical Substances Biomarkers ; Protein Kinase Inhibitors
    Language English
    Publishing date 2020-10-19
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2020.5772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Predicting transcription factor activity using prior biological information.

    Yashar, William M / Estabrook, Joseph / Holly, Hannah D / Somers, Julia / Nikolova, Olga / Babur, Özgün / Braun, Theodore P / Demir, Emek

    iScience

    2024  Volume 27, Issue 3, Page(s) 109124

    Abstract: Dysregulation of normal transcription factor activity is a common driver of disease. Therefore, the detection of aberrant transcription factor activity is important to understand disease pathogenesis. We have developed Priori, a method to predict ... ...

    Abstract Dysregulation of normal transcription factor activity is a common driver of disease. Therefore, the detection of aberrant transcription factor activity is important to understand disease pathogenesis. We have developed Priori, a method to predict transcription factor activity from RNA sequencing data. Priori has two key advantages over existing methods. First, Priori utilizes literature-supported regulatory information to identify transcription factor-target gene relationships. It then applies linear models to determine the impact of transcription factor regulation on the expression of its target genes. Second, results from a third-party benchmarking pipeline reveals that Priori detects aberrant activity from 124 single-gene perturbation experiments with higher sensitivity and specificity than 11 other methods. We applied Priori and other top-performing methods to predict transcription factor activity from two large primary patient datasets. Our work demonstrates that Priori uniquely discovered significant determinants of survival in breast cancer and identified mediators of drug response in leukemia.
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.109124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: sciMET-cap: High-throughput single-cell methylation analysis with a reduced sequencing burden.

    Acharya, Sonia N / Nichols, Ruth V / Rylaarsdam, Lauren E / O'Connell, Brendan L / Braun, Theodore P / Adey, Andrew C

    bioRxiv : the preprint server for biology

    2023  

    Abstract: DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature ... ...

    Abstract DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Sufficient off-target coverage further enables the production of near-complete methylomes for individual cell types. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).
    Language English
    Publishing date 2023-07-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.12.548718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Navigating Challenges in Monitoring Chronic Myeloid Leukemia with Multiple BCR-ABL1 Transcripts.

    Smith, Brittany M / Brewer, Diana / Druker, Brian J / Braun, Theodore P

    Case reports in oncology

    2021  Volume 14, Issue 3, Page(s) 1707–1711

    Abstract: Quantitative PCR-based strategies are typically effective for monitoring BCR-ABL1 transcript levels in chronic myeloid leukemia (CML). Additionally, some patients treated with tyrosine kinase inhibitors can experience long-term treatment-free remission ... ...

    Abstract Quantitative PCR-based strategies are typically effective for monitoring BCR-ABL1 transcript levels in chronic myeloid leukemia (CML). Additionally, some patients treated with tyrosine kinase inhibitors can experience long-term treatment-free remission after discontinuation of the inhibitor. However, this outcome hinges on effectively monitoring the patient's response to therapy. We present a patient with CML and multiple BCR-ABL1 transcripts, including a rare isoform that lacks qPCR standardization. We describe unexpected discrepancies in transcript quantification, further having an impact on clinical decision-making regarding duration of treatment. To better inform clinical practice, we suggest monitoring patients at the same testing facility to better track transcript trend.
    Language English
    Publishing date 2021-11-29
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2458961-5
    ISSN 1662-6575
    ISSN 1662-6575
    DOI 10.1159/000520400
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: BCR-ABL+ Chronic Myeloid Leukemia Arising in a Family With Inherited ANKRD26-Related Thrombocytopenia.

    Tsumura, Aaron M / Druker, Brian J / Brewer, Diana / Press, Richard / Braun, Theodore P

    JCO precision oncology

    2021  Volume 5

    MeSH term(s) Aged ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Male ; Middle Aged ; Thrombocytopenia/genetics
    Chemical Substances ANKRD26 protein, human ; Intercellular Signaling Peptides and Proteins
    Language English
    Publishing date 2021-02-19
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.20.00318
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: CITEViz: interactively classify cell populations in CITE-Seq via a flow cytometry-like gating workflow using R-Shiny.

    Kong, Garth L / Nguyen, Thai T / Rosales, Wesley K / Panikar, Anjali D / Cheney, John H W / Lusardi, Theresa A / Yashar, William M / Curtiss, Brittany M / Carratt, Sarah A / Braun, Theodore P / Maxson, Julia E

    BMC bioinformatics

    2024  Volume 25, Issue 1, Page(s) 142

    Abstract: Background: The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with ... ...

    Abstract Background: The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) simultaneously profiles the RNA transcriptome and the surface protein expression. The surface protein markers in CITE-Seq can be used to identify cell populations similar to the iterative filtration process in flow cytometry, also called "gating", and is an essential step for downstream analyses and data interpretation. While several packages allow users to interactively gate cells, they often do not process multi-omic sequencing datasets and may require writing redundant code to specify gate boundaries. To streamline the gating process, we developed CITEViz which allows users to interactively gate cells in Seurat-processed CITE-Seq data. CITEViz can also visualize basic quality control (QC) metrics allowing for a rapid and holistic evaluation of CITE-Seq data.
    Results: We applied CITEViz to a peripheral blood mononuclear cell CITE-Seq dataset and gated for several major blood cell populations (CD14 monocytes, CD4 T cells, CD8 T cells, NK cells, B cells, and platelets) using canonical surface protein markers. The visualization features of CITEViz were used to investigate cellular heterogeneity in CD14 and CD16-expressing monocytes and to detect differential numbers of detected antibodies per patient donor. These results highlight the utility of CITEViz to enable the robust classification of single cell populations.
    Conclusions: CITEViz is an R-Shiny app that standardizes the gating workflow in CITE-Seq data for efficient classification of cell populations. Its secondary function is to generate basic feature plots and QC figures specific to multi-omic data. The user interface and internal workflow of CITEViz uniquely work together to produce an organized workflow and sensible data structures for easy data retrieval. This package leverages the strengths of biologists and computational scientists to assess and analyze multi-omic single-cell datasets. In conclusion, CITEViz streamlines the flow cytometry gating workflow in CITE-Seq data to help facilitate novel hypothesis generation.
    MeSH term(s) Humans ; Software ; Sequence Analysis, RNA/methods ; Workflow ; Leukocytes, Mononuclear ; Flow Cytometry ; Membrane Proteins ; Single-Cell Analysis/methods ; Gene Expression Profiling/methods
    Chemical Substances Membrane Proteins
    Language English
    Publishing date 2024-04-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041484-5
    ISSN 1471-2105 ; 1471-2105
    ISSN (online) 1471-2105
    ISSN 1471-2105
    DOI 10.1186/s12859-024-05762-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: RUNX1::ETO translocations must precede CSF3R mutations to promote acute myeloid leukemia development.

    Carratt, Sarah A / Kong, Garth L / Coblentz, Cody / Schonrock, Zachary / Maloney, Lauren / Weeder, Ben / Yashar, Will / Callahan, Rowan / Blaylock, Hunter / Coleman, Colin / Coleman, Dan / Braun, Theodore P / Maxson, Julia E

    Leukemia

    2023  Volume 37, Issue 5, Page(s) 1141–1146

    MeSH term(s) Humans ; Core Binding Factor Alpha 2 Subunit/genetics ; Leukemia, Myeloid, Acute/genetics ; Mutation ; Receptors, Colony-Stimulating Factor/genetics ; Translocation, Genetic
    Chemical Substances Core Binding Factor Alpha 2 Subunit ; CSF3R protein, human ; Receptors, Colony-Stimulating Factor ; RUNX1 protein, human
    Language English
    Publishing date 2023-03-09
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-023-01862-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  9. Article: Outgrowth of a CSF3R-mutant clone drives a second myeloproliferative neoplasm in a chronic myeloid leukemia patient: a case report.

    Carratt, Sarah A / Brewer, Diana / Maxson, Julia E / Druker, Brian J / Braun, Theodore P

    Biomarker research

    2021  Volume 9, Issue 1, Page(s) 8

    Abstract: Background: Chronic myeloid leukemia (CML) and chronic neutrophilic leukemia (CNL) are two myeloproliferative neoplasms with mutually exclusive diagnostic criteria. A hallmark of CML is the Philadelphia chromosome (Ph), which results in a BCR-ABL1 ... ...

    Abstract Background: Chronic myeloid leukemia (CML) and chronic neutrophilic leukemia (CNL) are two myeloproliferative neoplasms with mutually exclusive diagnostic criteria. A hallmark of CML is the Philadelphia chromosome (Ph), which results in a BCR-ABL1 fusion gene and constitutive tyrosine kinase activity. CNL is a Ph-negative neoplasm and is defined in part by the presence of CSF3R mutations, which drive constative JAK/STAT signaling.
    Case presentation: Here, we report the exceedingly rare co-occurrence of two granulocytic myeloproliferative neoplasms in a 69-year old male patient. After an initial diagnosis of chronic myeloid leukemia, the patient's clinical course was shaped by hematologic toxicity, the emergence of treatment-resistant BCR-ABL1 clones, and the expansion of a CSF3R-mutant clone without ABL1 mutations under selective pressure from tyrosine kinase inhibitors. The emergence of the CSF3R-mutant, neutrophilic clone led to the diagnosis of CNL as a second myeloproliferative neoplasm in the same patient.
    Conclusions: This is the first reported case of CNL arising subsequent to CML, which occurred under selective pressure from targeted therapy in a patient with complex clonal architecture. Patients with such molecularly complex disease may ultimately benefit from combination therapy that targets multiple oncogenic pathways.
    Language English
    Publishing date 2021-01-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2699926-2
    ISSN 2050-7771
    ISSN 2050-7771
    DOI 10.1186/s40364-021-00261-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Correction: Mutant SETBP1 enhances NRAS-driven MAPK pathway activation to promote aggressive leukemia.

    Carratt, Sarah A / Braun, Theodore P / Coblentz, Cody / Schonrock, Zachary / Callahan, Rowan / Curtiss, Brittany M / Maloney, Lauren / Foley, Amy C / Maxson, Julia E

    Leukemia

    2022  Volume 36, Issue 8, Page(s) 2149

    Language English
    Publishing date 2022-07-06
    Publishing country England
    Document type Published Erratum
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-022-01646-6
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