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  1. Article ; Online: Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways.

    Prins, Marileen M / Verstockt, Bram / Ferrante, Marc / Vermeire, Séverine / Wildenberg, Manon E / Koelink, Pim J

    Frontiers in immunology

    2021  Volume 12, Page(s) 627535

    Abstract: The expression ... ...

    Abstract The expression of
    Language English
    Publishing date 2021-03-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.627535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Thiopurines correct the effects of autophagy impairment on intestinal healing - a potential role for ARHGAP18/RhoA.

    Prins, Marileen M C / Giugliano, Francesca P / van Roest, Manon / van de Graaf, Stan F J / Koelink, Pim J / Wildenberg, Manon E

    Disease models & mechanisms

    2021  Volume 14, Issue 4

    Abstract: The ATG16L1 T300A single-nucleotide polymorphism (SNP) is associated with Crohn's disease and causes an autophagy impairment. We have previously shown that this SNP is involved in the migration and hyperactivation of Rac1 in dendritic cells. Mucosal ... ...

    Abstract The ATG16L1 T300A single-nucleotide polymorphism (SNP) is associated with Crohn's disease and causes an autophagy impairment. We have previously shown that this SNP is involved in the migration and hyperactivation of Rac1 in dendritic cells. Mucosal healing, currently the main target for inflammatory bowel disease treatment, depends on restoration of the epithelial barrier and requires appropriate migration of epithelial cells towards and over mucosal lesions. Therefore, we here further investigated the impact of autophagy on epithelial migration. ATG16L1 knockdown was established in the HT29 human colonic epithelial cell line using lentiviral transduction. Migratory capacity was evaluated using scratch assays and RhoAGTP was measured using G-LISA. Immunofluorescent ARHGAP18 and sequestome 1 (SQSTM1; also known as p62) staining was performed on HT29 cells and primary colonic tissue of Crohn's disease patients. We observed that ATG16L1 knockdown cells exhibited decreased autophagy and decreased migration capacity. Furthermore, activity of RhoA was decreased. These characteristics were phenocopied using ATG5 knockdown and pharmacological inhibition of autophagy. The migration defect was dependent on accumulation of SQSTM1 and was alleviated upon SQSTM1 knockdown. Strikingly, thiopurines also mitigated the effects of impaired autophagy. RhoA dysregulation appeared mediated through accumulation of the upstream regulator ARHGAP18, which was observed in cell lines, human foetal organoids and primary colonic tissue. Our results indicate that the ATG16L1 T300A Crohn's disease-associated SNP causes a decrease in migration capacity in epithelial cells, mediated by an increase in SQSTM1 and ARHGAP18 protein and subsequent reduced RhoA activation.
    MeSH term(s) Autophagy/drug effects ; Cell Movement/drug effects ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; GTPase-Activating Proteins/metabolism ; HT29 Cells ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/pathology ; Intestines/drug effects ; Intestines/pathology ; Organoids/drug effects ; Organoids/metabolism ; Phenotype ; Sequestosome-1 Protein/metabolism ; Sulfhydryl Compounds/pharmacology ; Wound Healing/drug effects ; rhoA GTP-Binding Protein/metabolism
    Chemical Substances ARHGAP18 protein, human ; GTPase-Activating Proteins ; SQSTM1 protein, human ; Sequestosome-1 Protein ; Sulfhydryl Compounds ; rhoA GTP-Binding Protein (EC 3.6.5.2)
    Language English
    Publishing date 2021-04-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2451104-3
    ISSN 1754-8411 ; 1754-8403
    ISSN (online) 1754-8411
    ISSN 1754-8403
    DOI 10.1242/dmm.047233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Applicability of different cell line-derived dendritic cell-like cells in autophagy research

    Prins, Marileen M.C. / van Roest, Manon / Vermeulen, Jacqueline L.M. / Tjabringa, G. Sandra / van de Graaf, Stan F.J. / Koelink, Pim J. / Wildenberg, Manon E.

    Journal of immunological methods. 2021 Oct., v. 497

    2021  

    Abstract: Immortalized cell lines have been long used as substitute for ex vivo murine and human material, but exhibit features that are not found in healthy tissue. True human dendritic cells (DC) cannot be cultured or passaged as opposed to immortalized cell ... ...

    Abstract Immortalized cell lines have been long used as substitute for ex vivo murine and human material, but exhibit features that are not found in healthy tissue. True human dendritic cells (DC) cannot be cultured or passaged as opposed to immortalized cell lines. Research in the fields of immunogenic responses and immunotolerance in DCs has increased over the last decade. Autophagy has gained interest in these fields as well, and has been researched extensively in many other cell types as well. Here we have studied the applicability of cell line-derived dendritic cell-like cells of six myeloid cell lines aimed at research focussed on autophagy.Six myeloid leukaemia cell lines were differentiated towards cell line-derived dendritic cell-like cells (cd-DC) using GM-CSF, IL-4, Ionomycine and PMA: HL60, KG1, MM6, MV-4-11, THP1 and U937. Autophagy was modulated using Rapamycin, Bafilomycin A1 and 3MA. Cell lines were genotyped for autophagy-related SNPs using RFLP. Marker expression was determined with FACS analysis and cytokine profiles were determined using Human Cytometric Bead Assay. Antigen uptake was assessed using Fluoresbrite microspheres.All researched cell lines harboured SNPs in the autophagy pathways. MM6 and THP1 derived cd-DCs resembled monocyte-derived DCs (moDC) most closely in marker expression, cytokine profiles and autophagy response. The HL60 and U937 cell lines proved least suitable for autophagy-related dendritic cell research.The genetic background of cell lines should be taken into account upon studying (the effects of) autophagy in any cell line. Although none of the studied cell lines recapitulate the full spectrum of DC characteristics, MM6 and THP1 derived cd-DCs are most suitable for autophagy-related research in dendritic cells.
    Keywords antigens ; autophagy ; cell lines ; dendritic cells ; genetic background ; genotyping ; humans ; interleukin-4 ; mice ; myeloid leukemia ; rapamycin
    Language English
    Dates of publication 2021-10
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2021.113106
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Applicability of different cell line-derived dendritic cell-like cells in autophagy research.

    Prins, Marileen M C / van Roest, Manon / Vermeulen, Jacqueline L M / Tjabringa, G Sandra / van de Graaf, Stan F J / Koelink, Pim J / Wildenberg, Manon E

    Journal of immunological methods

    2021  Volume 497, Page(s) 113106

    Abstract: Background and aims: Immortalized cell lines have been long used as substitute for ex vivo murine and human material, but exhibit features that are not found in healthy tissue. True human dendritic cells (DC) cannot be cultured or passaged as opposed to ...

    Abstract Background and aims: Immortalized cell lines have been long used as substitute for ex vivo murine and human material, but exhibit features that are not found in healthy tissue. True human dendritic cells (DC) cannot be cultured or passaged as opposed to immortalized cell lines. Research in the fields of immunogenic responses and immunotolerance in DCs has increased over the last decade. Autophagy has gained interest in these fields as well, and has been researched extensively in many other cell types as well. Here we have studied the applicability of cell line-derived dendritic cell-like cells of six myeloid cell lines aimed at research focussed on autophagy.
    Methods: Six myeloid leukaemia cell lines were differentiated towards cell line-derived dendritic cell-like cells (cd-DC) using GM-CSF, IL-4, Ionomycine and PMA: HL60, KG1, MM6, MV-4-11, THP1 and U937. Autophagy was modulated using Rapamycin, Bafilomycin A1 and 3MA. Cell lines were genotyped for autophagy-related SNPs using RFLP. Marker expression was determined with FACS analysis and cytokine profiles were determined using Human Cytometric Bead Assay. Antigen uptake was assessed using Fluoresbrite microspheres.
    Results and discussion: All researched cell lines harboured SNPs in the autophagy pathways. MM6 and THP1 derived cd-DCs resembled monocyte-derived DCs (moDC) most closely in marker expression, cytokine profiles and autophagy response. The HL60 and U937 cell lines proved least suitable for autophagy-related dendritic cell research.
    Conclusion: The genetic background of cell lines should be taken into account upon studying (the effects of) autophagy in any cell line. Although none of the studied cell lines recapitulate the full spectrum of DC characteristics, MM6 and THP1 derived cd-DCs are most suitable for autophagy-related research in dendritic cells.
    MeSH term(s) Adenine/analogs & derivatives ; Adenine/pharmacology ; Autophagy/drug effects ; Autophagy/genetics ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism ; Cell Differentiation ; Cytokines/metabolism ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Flow Cytometry ; Genotype ; HL-60 Cells ; Humans ; Macrolides/pharmacology ; Microscopy, Fluorescence ; Monocytes/immunology ; Monocytes/metabolism ; Monocytes/pathology ; Phenotype ; Polymorphism, Single Nucleotide ; Sirolimus/pharmacology ; THP-1 Cells ; U937 Cells
    Chemical Substances Autophagy-Related Proteins ; Cytokines ; Macrolides ; 3-methyladenine (5142-23-4) ; bafilomycin A1 (88899-55-2) ; Adenine (JAC85A2161) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2021-07-26
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2021.113106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Endometrial SamPling befoRe or aftEr Saline infusion SOnography (ESPRESSO Trial): a national survey and a study protocol of a multicenter RCT.

    Vroom, Albertine J / Prins, Marileen M / Bongers, Marlies Y / Geomini, Peggy M / Timmermans, Anne / Hanegem, Nehallenia van

    Minerva ginecologica

    2017  Volume 69, Issue 3, Page(s) 304–308

    Abstract: Postmenopausal bleeding can be the first clinical sign of an endometrial abnormality. Because of an increased risk of malignancy, evaluation is advocated. Polyps are reported up to 40% in women with postmenopausal bleeding. These polyps carry a risk of 6% ...

    Abstract Postmenopausal bleeding can be the first clinical sign of an endometrial abnormality. Because of an increased risk of malignancy, evaluation is advocated. Polyps are reported up to 40% in women with postmenopausal bleeding. These polyps carry a risk of 6% for a focal (pre-) malignancy. To perform complete diagnostic work-up, recent guidelines recommend endometrial sampling and a saline infusion sonography if a previous transvaginal ultrasound shows an endometrial thickness of more than 4 mm. The current guideline shows no consensus of the sequence of both diagnostic procedures. Hypothetically, the fluid of the saline infusion sonography (SIS) could affect the quality of the endometrial sample. We designed a randomized trial (the ESPRESSO Trial; Trial Registration No. NTR5690) to investigate the quality of the endometrial sample (Pipelle®) when performed before or after SIS in postmenopausal women. We will perform a randomized trial comparing two diagnostic work-ups (SIS and subsequent Pipelle® versus Pipelle® and subsequent SIS) in women with postmenopausal bleeding. The study will be performed in one teaching and one Academic hospital in the Netherlands. Women with postmenopausal bleeding and an endometrial thickness of more than 4 mm are eligible. The gynecologist will evaluate quality of the SIS and the quality of the Pipelle® will be evaluated by a pathologist (possible to diagnose or not). Furthermore, the incidence and intensity of pain will be evaluated. The results will give insight whether the quality of the Pipelle® is influenced by the SIS or not.
    MeSH term(s) Endometrial Neoplasms/diagnosis ; Endometrium/diagnostic imaging ; Endometrium/pathology ; Female ; Humans ; Netherlands ; Polyps/pathology ; Postmenopause ; Research Design ; Sodium Chloride/administration & dosage ; Time Factors ; Ultrasonography/methods ; Uterine Hemorrhage/diagnostic imaging ; Uterine Hemorrhage/etiology
    Chemical Substances Sodium Chloride (451W47IQ8X)
    Language English
    Publishing date 2017-06
    Publishing country Italy
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 80159-8
    ISSN 1827-1650 ; 0026-4784 ; 0325-8793
    ISSN (online) 1827-1650
    ISSN 0026-4784 ; 0325-8793
    DOI 10.23736/S0026-4784.17.04014-X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis.

    van Hanegem, Nehalennia / Prins, Marileen M C / Bongers, Marlies Y / Opmeer, Brent C / Sahota, Daljit Singh / Mol, Ben Willem J / Timmermans, Anne

    European journal of obstetrics, gynecology, and reproductive biology

    2016  Volume 197, Page(s) 147–155

    Abstract: Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses ... ...

    Abstract Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with postmenopausal bleeding, the sensitivity of endometrial sampling to detect endometrial cancer and especially atypical hyperplasia and endometrial disease, including endometrial polyps, is lower than previously thought. Therefore, further diagnostic work-up for focal pathology is warranted, after a benign result of endometrial sampling.
    MeSH term(s) Biopsy ; Dilatation and Curettage ; Endometrial Hyperplasia/complications ; Endometrial Hyperplasia/diagnosis ; Endometrial Neoplasms/complications ; Endometrial Neoplasms/diagnosis ; Endometrium/pathology ; Female ; Humans ; Hysteroscopy ; Polyps/complications ; Polyps/diagnosis ; Postmenopause ; Sensitivity and Specificity ; Uterine Diseases/complications ; Uterine Diseases/diagnosis ; Uterine Hemorrhage/diagnosis ; Uterine Hemorrhage/etiology
    Language English
    Publishing date 2016-02
    Publishing country Ireland
    Document type Journal Article ; Meta-Analysis ; Review
    ZDB-ID 190605-7
    ISSN 1872-7654 ; 0301-2115 ; 0028-2243
    ISSN (online) 1872-7654
    ISSN 0301-2115 ; 0028-2243
    DOI 10.1016/j.ejogrb.2015.12.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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