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  1. Article ; Online: Corrigendum: Detection of Apoptotic Cells Using Propidium Iodide Staining.

    Newbold, Andrea / Martin, Ben P / Cullinane, Carleen / Bots, Michael

    Cold Spring Harbor protocols

    2018  Volume 2018, Issue 6, Page(s) Corr104943

    Language English
    Publishing date 2018-06-01
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 1559-6095
    ISSN (online) 1559-6095
    DOI 10.1101/pdb.corr104943
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Correction to: Combining the differentiating effect of panobinostat with the apoptotic effect of arsenic trioxide leads to significant survival benefit in a model of t(8;21) acute myeloid leukemia.

    Salmon, Jessica M / Bots, Michael / Vidacs, Eva / Stanley, Kym L / Atadja, Peter / Zuber, Johannes / Johnstone, Ricky W

    Clinical epigenetics

    2020  Volume 12, Issue 1, Page(s) 178

    Abstract: An amendment to this paper has been published and can be accessed via the original article. ...

    Abstract An amendment to this paper has been published and can be accessed via the original article.
    Language English
    Publishing date 2020-11-18
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 2553921-8
    ISSN 1868-7083 ; 1868-7075
    ISSN (online) 1868-7083
    ISSN 1868-7075
    DOI 10.1186/s13148-020-00964-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Rational combinations using HDAC inhibitors.

    Bots, Michael / Johnstone, Ricky W

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2009  Volume 15, Issue 12, Page(s) 3970–3977

    Abstract: In addition to well-characterized genetic abnormalities that lead to cancer onset and progression, it is now recognized that alterations to the epigenome may also play a significant role in oncogenesis. As a result, epigenetic-modulating agents such as ... ...

    Abstract In addition to well-characterized genetic abnormalities that lead to cancer onset and progression, it is now recognized that alterations to the epigenome may also play a significant role in oncogenesis. As a result, epigenetic-modulating agents such as histone deacetylase inhibitors (HDACi) have attracted enormous attention as anticancer drugs. In numerous in vitro and preclinical settings, these compounds have shown their vast potential as single agent anticancer therapies, but unfortunately equivalent responses have not always been observed in patients. Given the pleiotropic effects HDACi have on malignant cells, their true therapeutic potential most likely lies in combination with other anticancer drugs. In this review we will focus on the anticancer effects of HDACi when combined with other cancer therapeutics with an emphasis on those combinations based on a strong molecular rationale.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Apoptosis Regulatory Proteins/metabolism ; Clinical Trials as Topic ; Enzyme Inhibitors/therapeutic use ; Histone Deacetylase Inhibitors ; Humans ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/genetics ; Neoplasms/drug therapy ; Neoplasms/genetics
    Chemical Substances Antineoplastic Agents ; Apoptosis Regulatory Proteins ; Enzyme Inhibitors ; Histone Deacetylase Inhibitors
    Language English
    Publishing date 2009-06-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-08-2786
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Serpins in T cell immunity.

    Bots, Michael / Medema, Jan Paul

    Journal of leukocyte biology

    2008  Volume 84, Issue 5, Page(s) 1238–1247

    Abstract: Serine protease inhibitors (serpins) are a family of proteins that are important in the regulation of several biological processes. This mainly involves the inhibition of serine proteases, although some serpins inhibit a different class of proteases or ... ...

    Abstract Serine protease inhibitors (serpins) are a family of proteins that are important in the regulation of several biological processes. This mainly involves the inhibition of serine proteases, although some serpins inhibit a different class of proteases or even function without inhibitory activity. In contrast to other protease inhibitor families, serpins inhibit their target proteases by a specific mechanism, which depends on a change in conformation. This review primarily focuses on one subgroup of serpins--ovalbumin (ov)-serpins. Different than most members of the family, this group of serpins lacks secretion signal sequences and therefore, mainly functions intracellularly. In addition to expression in most normal tissues, ov-serpins can be found in multiple different cells of the immune system. Interestingly, expression of ov-serpins in these cells is tightly regulated, indicating a role for these serpins in the regulation of immune responses. The role of serpins in the immune response will be the topic of this review.
    MeSH term(s) CD8-Positive T-Lymphocytes/immunology ; Humans ; Immunologic Memory ; Neoplasms/immunology ; Ovalbumin/physiology ; Serpins/immunology ; Serpins/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
    Chemical Substances Serpins ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2008-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1189/jlb.0208140
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Discovery of biomarkers for the presence and progression of left ventricular diastolic dysfunction and HEart faiLure with Preserved ejection Fraction in patients at risk for cardiovascular disease: rationale and design of the HELPFul case-cohort study in a Dutch cardiology outpatient clinic.

    Valstar, Gideon B / Bots, Sophie H / Groepenhoff, Floor / Gohar, Aisha / Rutten, Frans H / Leiner, Tim / Cramer, Maarten Jan Maria / Teske, Arco J / Suciadi, Leonardo P / Menken, Roxana / Pasterkamp, Gerard / Asselbergs, Folkert W / Hofstra, Leonard / Bots, Michael L / den Ruijter, Hester M

    BMJ open

    2019  Volume 9, Issue 6, Page(s) e028408

    Abstract: Introduction: Left ventricular diastolic dysfunction (LVDD) is a common condition in both sexes that may deteriorate into heart failure (HF) with preserved ejection fraction (pEF), although this seems to happen more often in women than in men. Both LVDD ...

    Abstract Introduction: Left ventricular diastolic dysfunction (LVDD) is a common condition in both sexes that may deteriorate into heart failure (HF) with preserved ejection fraction (pEF), although this seems to happen more often in women than in men. Both LVDD and HFpEF often go unrecognised, necessitating the discovery of biomarkers that aid both the identification of individuals with LVDD at risk of developing HF and identification of individuals most likely to benefit from treatment.
    Methods and analysis: HELPFul is an ongoing case-cohort study at a Dutch cardiology outpatient clinic enrolling patients aged 45 years and older without history of cardiovascular disease, who were referred by the general practitioner for cardiac evaluation. We included a random sample of patients and enriched the cohort with cases (defined as an E/e' ≥8 measured with echocardiography). Information about medical history, cardiovascular risk factors, electrocardiography, echocardiography, exercise test performance, common carotid intima-media thickness measurement and standard cardiovascular biomarkers was obtained from the routine care data collected by the cardiology outpatient clinic. Study procedure consists of extensive venous blood collection for biobanking and additional standardised questionnaires. Follow-up will consist of standardised questionnaires by mail and linkage to regional and national registries. We will perform cardiac magnetic resonance imaging and coronary CT angiography in a subgroup of patients to investigate the extent of macrovascular and microvascular coronary disease.
    Ethics and dissemination: The study protocol was approved by the Institutional Review Board of the University Medical Center Utrecht. Results will be disseminated through national and international conferences and in peer-reviewed journals in cardiovascular disease.
    Trial registration: NTR6016;Pre-results.
    MeSH term(s) Ambulatory Care Facilities ; Biomarkers ; Cardiology/methods ; Carotid Intima-Media Thickness/statistics & numerical data ; Cohort Studies ; Disease Progression ; Echocardiography/statistics & numerical data ; Exercise Test/statistics & numerical data ; Female ; Heart Failure/diagnosis ; Heart Failure/physiopathology ; Humans ; Male ; Middle Aged ; Netherlands ; Prospective Studies ; Risk ; Ventricular Dysfunction, Left/diagnosis ; Ventricular Dysfunction, Left/physiopathology
    Chemical Substances Biomarkers
    Language English
    Publishing date 2019-06-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2018-028408
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Detection of apoptotic cells using immunohistochemistry.

    Newbold, Andrea / Martin, Ben P / Cullinane, Carleen / Bots, Michael

    Cold Spring Harbor protocols

    2014  Volume 2014, Issue 11, Page(s) 1196–1201

    Abstract: Immunohistochemistry is commonly used to show the presence of apoptotic cells in situ. In this protocol, B-cell lymphoma cells are injected into recipient mice and, on tumor formation, the mice are treated with the apoptosis inducer vorinostat (a histone ...

    Abstract Immunohistochemistry is commonly used to show the presence of apoptotic cells in situ. In this protocol, B-cell lymphoma cells are injected into recipient mice and, on tumor formation, the mice are treated with the apoptosis inducer vorinostat (a histone deacetylase inhibitor). Tumor samples are fixed and sectioned, and fragmented DNA (a feature of apoptotic cells) is end-labeled by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Immunohistochemical methods are then used to detect the labeled DNA and identify B-cell lymphoma cells in the last stage of apoptosis. Because the assay can lead to false-positive results, it is advisable to carry out an additional assay (e.g., immunohistochemistry for active caspase-3) to confirm the presence of apoptotic cells.
    MeSH term(s) Animals ; Apoptosis ; DNA/analysis ; DNA Fragmentation ; Histone Deacetylase Inhibitors/administration & dosage ; Hydroxamic Acids/administration & dosage ; Immunohistochemistry/methods ; In Situ Nick-End Labeling ; Lymphoma, B-Cell/pathology ; Mice
    Chemical Substances Histone Deacetylase Inhibitors ; Hydroxamic Acids ; vorinostat (58IFB293JI) ; DNA (9007-49-2)
    Language English
    Publishing date 2014-11-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1559-6095
    ISSN (online) 1559-6095
    DOI 10.1101/pdb.prot082537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Measuring apoptosis in mammals in vivo.

    Newbold, Andrea / Martin, Ben P / Cullinane, Carleen / Bots, Michael

    Cold Spring Harbor protocols

    2014  Volume 2014, Issue 11, Page(s) 1125–1127

    Abstract: Apoptosis is a mode of cell death that is essential in multicellular organisms for the removal of superfluous, damaged, or potentially dangerous cells during development, infection, or normal tissue homeostasis. To prevent inflammation, cells undergoing ... ...

    Abstract Apoptosis is a mode of cell death that is essential in multicellular organisms for the removal of superfluous, damaged, or potentially dangerous cells during development, infection, or normal tissue homeostasis. To prevent inflammation, cells undergoing apoptosis produce "find-me" signals that trigger the recruitment of phagocytes, which clear the apoptotic cells on recognition of "eat-me" signals. Despite the loss of billions of cells per day by apoptosis in the human body, the number of apoptotic cells found in healthy tissue is surprisingly low and reflects the efficiency of this process. However, in certain conditions (e.g., in cancer cells responding to chemotherapy), the number of apoptotic cells is too high to be efficiently cleared by phagocytes, and apoptotic cells can be observed. In these situations, the detection of apoptosis may be helpful in monitoring disease progression as well as in predicting the responses of tumors to anticancer therapies. Here we introduce various methods for monitoring apoptotic cells in vivo using a murine model of B-cell lymphoma and a solid tumor xenograft.
    MeSH term(s) Animals ; Apoptosis ; Heterografts/pathology ; Lymphoma, B-Cell/pathology ; Mice ; Neoplasm Transplantation
    Language English
    Publishing date 2014-11-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1559-6095
    ISSN (online) 1559-6095
    DOI 10.1101/pdb.top070417
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Fluorodeoxyglucose-based positron emission tomography imaging to monitor drug responses in solid tumors.

    Newbold, Andrea / Martin, Ben P / Cullinane, Carleen / Bots, Michael

    Cold Spring Harbor protocols

    2014  Volume 2014, Issue 10, Page(s) pdb.prot082529

    Abstract: Positron emission tomography (PET) is used to monitor the uptake of the labeled glucose analogue fluorodeoxyglucose (¹⁸F-FDG) by solid tumor cells, a process generally believed to reflect viable tumor cell mass. The use of ¹⁸F-FDG exploits the high ... ...

    Abstract Positron emission tomography (PET) is used to monitor the uptake of the labeled glucose analogue fluorodeoxyglucose (¹⁸F-FDG) by solid tumor cells, a process generally believed to reflect viable tumor cell mass. The use of ¹⁸F-FDG exploits the high demand for glucose in tumor cells, and serves to document over time the response of a solid tumor to an inducer of apoptosis. The apoptosis inducer crizotinib is a small-molecule inhibitor of c-Met, a receptor tyrosine kinase that is often dysregulated in human tumors. In this protocol, we describe how to monitor the response of a solid tumor to crizotinib. Human gastric tumor cells (GTL-16 cells) are injected into recipient mice and, on tumor formation, the mice are treated with crizotinib. The tracer ¹⁸F-FDG is then injected into the mice at several time points, and its uptake is monitored using PET. Because ¹⁸F-FDG uptake varies widely among different tumor models, preliminary experiments should be performed with each new model to determine its basal level of ¹⁸F-FDG uptake. Verifying that the basal level of uptake is sufficiently above background levels will assure accurate quantitation. Because ¹⁸F-FDG uptake is not a direct measure of apoptosis, it is advisable to carry out an additional direct method to show the presence of apoptotic cells.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Disease Models, Animal ; Fluorodeoxyglucose F18 ; Humans ; Mice ; Positron-Emission Tomography ; Pyrazoles/therapeutic use ; Pyridines/therapeutic use ; Stomach Neoplasms/diagnostic imaging ; Stomach Neoplasms/drug therapy ; Xenograft Model Antitumor Assays
    Chemical Substances Antineoplastic Agents ; Pyrazoles ; Pyridines ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; crizotinib (53AH36668S)
    Language English
    Publishing date 2014-10-01
    Publishing country United States
    Document type Journal Article
    ISSN 1559-6095
    ISSN (online) 1559-6095
    DOI 10.1101/pdb.prot082529
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Fluorodeoxyglucose-based positron emission tomography imaging to monitor drug responses in hematological tumors.

    Newbold, Andrea / Martin, Ben P / Cullinane, Carleen / Bots, Michael

    Cold Spring Harbor protocols

    2014  Volume 2014, Issue 10, Page(s) pdb.prot082511

    Abstract: Positron emission tomography (PET) can be used to monitor the uptake of the labeled glucose analog fluorodeoxyglucose (¹⁸F-FDG), a process that is generally believed to reflect viable tumor cell mass. The use of ¹⁸F-FDG PET can be helpful in documenting ... ...

    Abstract Positron emission tomography (PET) can be used to monitor the uptake of the labeled glucose analog fluorodeoxyglucose (¹⁸F-FDG), a process that is generally believed to reflect viable tumor cell mass. The use of ¹⁸F-FDG PET can be helpful in documenting over time the reduction in tumor mass volume in response to anticancer drug therapy in vivo. In this protocol, we describe how to monitor the response of murine B-cell lymphomas to an inducer of apoptosis, the anticancer drug vorinostat (a histone deacetylase inhibitor). B-cell lymphoma cells are injected into recipient mice and, on tumor formation, the mice are treated with vorinostat. The tracer ¹⁸F-FDG is then injected into the mice at several time points, and its uptake is monitored using PET. Because the uptake of ¹⁸F-FDG is not a direct measure of apoptosis, an additional direct method proving that apoptotic cells are present should also be performed.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Fluorodeoxyglucose F18 ; Humans ; Hydroxamic Acids/therapeutic use ; Lymphoma, B-Cell/diagnostic imaging ; Lymphoma, B-Cell/drug therapy ; Mice ; Mice, Inbred C57BL ; Positron-Emission Tomography ; Xenograft Model Antitumor Assays
    Chemical Substances Antineoplastic Agents ; Hydroxamic Acids ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; vorinostat (58IFB293JI)
    Language English
    Publishing date 2014-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1559-6095
    ISSN (online) 1559-6095
    DOI 10.1101/pdb.prot082511
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Detection of apoptotic cells using propidium iodide staining.

    Newbold, Andrea / Martin, Ben P / Cullinane, Carleen / Bots, Michael

    Cold Spring Harbor protocols

    2014  Volume 2014, Issue 11, Page(s) 1202–1206

    Abstract: Flow cytometry assays are often used to detect apoptotic cells in in vitro cultures. Depending on the experimental model, these assays can also be useful in evaluating apoptosis in vivo. In this protocol, we describe a propidium iodide (PI) flow ... ...

    Abstract Flow cytometry assays are often used to detect apoptotic cells in in vitro cultures. Depending on the experimental model, these assays can also be useful in evaluating apoptosis in vivo. In this protocol, we describe a propidium iodide (PI) flow cytometry assay to evaluate B-cell lymphomas that have undergone apoptosis in vivo. B-cell lymphoma cells are injected into recipient mice and, on tumor formation, the mice are treated with the apoptosis inducer vorinostat (a histone deacetylase inhibitor). Tumor samples collected from the lymph nodes and/or the spleen are used to prepare a single-cell suspension that is exposed to a hypotonic solution containing the fluorochrome PI. The DNA content of the cells, now labeled with PI, is analyzed by flow cytometry. Nuclear DNA content is lost during apoptosis, resulting in a hypodiploid (or sub-G1) DNA profile during flow cytometry. In contrast, healthy cells display a sharp diploid DNA profile.
    MeSH term(s) Animals ; Apoptosis ; DNA/analysis ; Flow Cytometry/methods ; Histone Deacetylase Inhibitors/administration & dosage ; Hydroxamic Acids/administration & dosage ; Lymphoma, B-Cell/pathology ; Mice ; Propidium/metabolism ; Staining and Labeling/methods
    Chemical Substances Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Propidium (36015-30-2) ; vorinostat (58IFB293JI) ; DNA (9007-49-2)
    Language English
    Publishing date 2014-11-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1559-6095
    ISSN (online) 1559-6095
    DOI 10.1101/pdb.prot082545
    Database MEDical Literature Analysis and Retrieval System OnLINE

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