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  1. AU="van Houdt, Inge S"
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  1. Article ; Online: Tetraspanin CD37 protects against the development of B cell lymphoma.

    de Winde, Charlotte M / Veenbergen, Sharon / Young, Ken H / Xu-Monette, Zijun Y / Wang, Xiao-Xiao / Xia, Yi / Jabbar, Kausar J / van den Brand, Michiel / van der Schaaf, Alie / Elfrink, Suraya / van Houdt, Inge S / Gijbels, Marion J / van de Loo, Fons A J / Bennink, Miranda B / Hebeda, Konnie M / Groenen, Patricia J T A / van Krieken, J Han / Figdor, Carl G / van Spriel, Annemiek B

    The Journal of clinical investigation

    2016  Volume 126, Issue 2, Page(s) 653–666

    Abstract: Worldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy and represents a substantial clinical problem. The molecular events that lead to B cell lymphoma are only partially defined. Here, we have provided evidence that ... ...

    Abstract Worldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy and represents a substantial clinical problem. The molecular events that lead to B cell lymphoma are only partially defined. Here, we have provided evidence that deficiency of tetraspanin superfamily member CD37, which is important for B cell function, induces the development of B cell lymphoma. Mice lacking CD37 developed germinal center-derived B cell lymphoma in lymph nodes and spleens with a higher incidence than Bcl2 transgenic mice. We discovered that CD37 interacts with suppressor of cytokine signaling 3 (SOCS3); therefore, absence of CD37 drives tumor development through constitutive activation of the IL-6 signaling pathway. Moreover, animals deficient for both Cd37 and Il6 were fully protected against lymphoma development, confirming the involvement of the IL-6 pathway in driving tumorigenesis. Loss of CD37 on neoplastic cells in patients with diffuse large B cell lymphoma (DLBCL) directly correlated with activation of the IL-6 signaling pathway and with worse progression-free and overall survival. Together, this study identifies CD37 as a tumor suppressor that directly protects against B cell lymphomagenesis and provides a strong rationale for blocking the IL-6 pathway in patients with CD37- B cell malignancies as a possible therapeutic intervention.
    MeSH term(s) Animals ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Germinal Center/metabolism ; Germinal Center/pathology ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Lymphoma, Large B-Cell, Diffuse/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Tetraspanins/genetics ; Tetraspanins/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
    Chemical Substances Antigens, CD ; Antigens, Neoplasm ; Cd37 protein, mouse ; Interleukin-6 ; Tetraspanins ; Tumor Suppressor Proteins
    Language English
    Publishing date 2016-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI81041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ua VI Zs.184: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression.

    van Houdt, Inge S / Sluijter, Berbel J R / Moesbergen, Laura M / Vos, Wim M / de Gruijl, Tanja D / Molenkamp, Barbara G / van den Eertwegh, Alfons J M / Hooijberg, Erik / van Leeuwen, Paul A M / Meijer, Chris J L M / Oudejans, Joost J

    International journal of cancer

    2008  Volume 123, Issue 3, Page(s) 609–615

    Abstract: In this study we investigated whether the presence of specific populations of tumor infiltrating lymphocytes (TILs) in diagnostic primary melanoma biopsies are related to outcome in clinically stage II melanoma patients. Moreover, we investigated whether ...

    Abstract In this study we investigated whether the presence of specific populations of tumor infiltrating lymphocytes (TILs) in diagnostic primary melanoma biopsies are related to outcome in clinically stage II melanoma patients. Moreover, we investigated whether the presence of TILs correlates with expression of MHC class I antigen and MHC class II antigen on tumor cells and/or tumor infiltrating antigen presenting cells. Diagnostic primary melanoma samples of 15 patients with an unfavorable outcome were compared with 20 patients with favorable outcome. Patients were matched for age, gender and Breslow thickness. Biopsies were examined for the presence of granzyme B+, CD8+, CD4+ and CD56+ TILs and for expression of MHC class I antigen and MHC class II antigen on tumor and/or tumor infiltrating cells. A favorable clinical outcome was strongly associated with the presence of GrB+ and CD4+ TILs, with expression of MHC class I antigen on tumor cells and with expression of MHC class II antigen on intratumoral antigen presenting cells. These data strongly support the notion that in melanoma patients the cellular immune response is a major factor in preventing melanoma cell dissemination.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antigen-Presenting Cells/immunology ; Biomarkers, Tumor/analysis ; Biopsy ; CD4 Antigens/analysis ; CD56 Antigen/analysis ; CD8 Antigens/analysis ; Female ; Granzymes/analysis ; Histocompatibility Antigens Class I/analysis ; Histocompatibility Antigens Class II/analysis ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Lymphocyte Activation ; Lymphocytes, Tumor-Infiltrating ; Male ; Melanoma/immunology ; Melanoma/pathology ; Middle Aged ; Neoplasm Staging ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology ; Treatment Outcome
    Chemical Substances Biomarkers, Tumor ; CD4 Antigens ; CD56 Antigen ; CD8 Antigens ; Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II ; Granzymes (EC 3.4.21.-)
    Language English
    Publishing date 2008-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.23543
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 478: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 576: Show issues

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  3. Article: Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with beta-tryptase monomers.

    Strik, Merel C M / Wolbink, Angela / Wouters, Dorine / Bladergroen, Bellinda A / Verlaan, Angelique R / van Houdt, Inge S / Hijlkema, Sanne / Hack, C Erik / Kummer, J Alain

    Blood

    2003  Volume 103, Issue 7, Page(s) 2710–2717

    Abstract: SERPINB6 (PI6) is a member of the intracellular serine protease inhibitors (serpins). Previous studies showed that SERPINB6 is localized mainly in the cytoplasm of endothelial cells, some epithelial cells, monocytes, and neutrophils. In these cells ... ...

    Abstract SERPINB6 (PI6) is a member of the intracellular serine protease inhibitors (serpins). Previous studies showed that SERPINB6 is localized mainly in the cytoplasm of endothelial cells, some epithelial cells, monocytes, and neutrophils. In these cells SERPINB6 is thought to prevent cellular damage by scavenging leaking lysosomal proteases. We show here, using novel, well-defined monoclonal antibodies, that SERPINB6 is abundantly expressed by mast cells in all organs and by the human mast cell line HMC-1. Gel filtration experiments revealed that the latter cells contain a high-molecular-weight form of SERPINB6, which consists of sodium dodecyl sulfate (SDS)-stable complexes of this inhibitor with monomeric beta-tryptase. Expression of SERPINB6 by mast cells was compared with those of tryptase and CD117 (c-kit) in biopsies from patients with different forms of mast cell disease. In all cases the lesional mast cells expressed SERPINB6, and, in diffuse cutaneous mastocytosis and mastocytoma, SERPINB6 was expressed by a substantially higher number of mast cells when compared with tryptase. In conclusion, SERPINB6 is abundantly expressed by normal mast cells and by mast cells in mastocytoma lesions. We suggest that in mast cells, SERPINB6 serves to regulate the activity of endogenous beta-tryptase in the cytoplasm.
    MeSH term(s) Cell Line ; Cloning, Molecular ; Cytoplasm/enzymology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Mast Cells/immunology ; Mastocytosis/immunology ; Plasmids ; Serine Endopeptidases/metabolism ; Serpins/genetics ; Serpins/metabolism ; Transfection ; Tryptases
    Chemical Substances Serpins ; serpin B6 ; Serine Endopeptidases (EC 3.4.21.-) ; Tryptases (EC 3.4.21.59)
    Language English
    Publishing date 2003-12-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2003-08-2981
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 364: Show issues

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  4. Article: Expression of the apoptosis inhibitor protease inhibitor 9 predicts clinical outcome in vaccinated patients with stage III and IV melanoma.

    van Houdt, Inge S / Oudejans, Joost J / van den Eertwegh, Alfonsus J M / Baars, Arnold / Vos, Wim / Bladergroen, Bellinda A / Rimoldi, Donata / Muris, Jettie J F / Hooijberg, Erik / Gundy, Chad M / Meijer, Chris J L M / Kummer, Jean A

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

    2005  Volume 11, Issue 17, Page(s) 6400–6407

    Abstract: Purpose: There have been reports of successful treatment of metastatic melanoma patients with active specific immunotherapy (ASI) using irradiated autologous tumor cell vaccination. It is still unknown why some patients respond and others do not. Tumor ... ...

    Abstract Purpose: There have been reports of successful treatment of metastatic melanoma patients with active specific immunotherapy (ASI) using irradiated autologous tumor cell vaccination. It is still unknown why some patients respond and others do not. Tumor cells can evade the immune system, for example through interference with antigen presentation by down-regulation of MHC molecules or expressing proteins interfering with cytotoxic lymphocyte-induced apoptosis like the granzyme B antagonist protease inhibitor 9 (PI-9).
    Experimental design: PI-9 expression was detected in melanoma cell lines. To investigated if PI-9 is important in the response to ASI, paraffin-embedded tissues from stage III or IV melanoma patients were stained.
    Results: PI-9 is expressed in melanoma cells and expression in metastasized melanoma cells is, in this group of patients, an adverse prognostic marker with regard to overall and disease-free survival. Moreover, loss of MHC-1 expression frequently occurs during tumor progression but is not associated with poor clinical outcome. Interestingly, melanoma patients with a favorable clinical outcome after ASI therapy usually have high percentages of activated (granzyme B-positive) tumor-infiltrating lymphocytes at time of first diagnosis and low percentages of activated lymphocytes at time of recurrent tumor.
    Conclusions: Expression of PI-9 in metastatic melanoma cells is associated with unfavorable clinical outcome whereas MHC-1 down-regulation is not. Although it cannot be proven that PI-9 expression is directly responsible for failure of immunotherapy, these data suggest that expression of PI-9 could be an important immune escape mechanism and that modulation of this inhibitor may enhance the efficacy of immunotherapy.
    MeSH term(s) Adult ; Aged ; Apoptosis ; Blotting, Western ; Cancer Vaccines/therapeutic use ; Disease-Free Survival ; Female ; Genes, MHC Class I/physiology ; Granzymes ; Humans ; Immunoenzyme Techniques ; Immunotherapy ; Lymphocyte Activation ; Lymphocytes, Tumor-Infiltrating/pathology ; Male ; Melanoma/immunology ; Melanoma/secondary ; Melanoma/therapy ; Middle Aged ; Neoplasm Staging ; Serine Endopeptidases/chemistry ; Serpins/metabolism ; Skin Neoplasms/immunology ; Skin Neoplasms/secondary ; Skin Neoplasms/therapy ; Survival Rate ; Treatment Outcome ; Tumor Cells, Cultured
    Chemical Substances Cancer Vaccines ; SERPINB9 protein, human ; Serpins ; GZMB protein, human (EC 3.4.21.-) ; Granzymes (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-)
    Language English
    Publishing date 2005-09-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-05-0306
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article: Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas.

    Muris, Jettie J F / Cillessen, Saskia A G M / Vos, Wim / van Houdt, Inge S / Kummer, J Alain / van Krieken, Johan H J M / Jiwa, N Mehdi / Jansen, Patty M / Kluin-Nelemans, Hanneke C / Ossenkoppele, Gert J / Gundy, Chad / Meijer, Chris J L M / Oudejans, Joost J

    Blood

    2004  Volume 105, Issue 7, Page(s) 2916–2923

    Abstract: We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoptosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c- ... ...

    Abstract We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoptosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c-Flip) and numbers of active caspase 3-positive lymphoma cells were used to determine the status of the caspase 8-mediated pathway. Expression levels of Bcl-2 and X-linked inhibitor of apoptosis (XIAP) were used to determine the status of the caspase 9-mediated pathway. Expression of c-Flip, XIAP, Bcl-2, and caspase 3 activity all provided prognostic information. According to these immunohistochemical parameters, inhibition of either or both caspase signaling pathways was detected in all patients. Three groups of patients were identified, one with a caspase 8 inhibition profile, one with caspase 8 and 9 inhibition profiles, and one with a caspase 9 inhibition profile. Caspase 9 inhibition was strongly associated with poor response to chemotherapy and usually with fatal outcome, whereas caspase 8 inhibition was associated with excellent clinical outcome. Thus, our data strongly suggest that inhibition of the caspase 9-mediated pathway, but not the caspase 8-mediated pathway, is a major cause for therapy resistance in patients with nodal DLBCL.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Phytogenic/administration & dosage ; Apoptosis/drug effects ; Apoptosis/physiology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Caspases/metabolism ; Etoposide/administration & dosage ; Female ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/metabolism ; Lymphoma, B-Cell/drug therapy ; Lymphoma, B-Cell/metabolism ; Lymphoma, B-Cell/mortality ; Lymphoma, B-Cell/pathology ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Lymphoma, Large B-Cell, Diffuse/mortality ; Lymphoma, Large B-Cell, Diffuse/pathology ; Male ; Middle Aged ; Poly(ADP-ribose) Polymerases/metabolism ; Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction/physiology ; Treatment Outcome ; X-Linked Inhibitor of Apoptosis Protein
    Chemical Substances Antineoplastic Agents, Phytogenic ; CASP8 and FADD-Like Apoptosis Regulating Protein ; CFLAR protein, human ; Intracellular Signaling Peptides and Proteins ; Proteins ; Proto-Oncogene Proteins c-bcl-2 ; X-Linked Inhibitor of Apoptosis Protein ; XIAP protein, human ; Etoposide (6PLQ3CP4P3) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; CASP3 protein, human (EC 3.4.22.-) ; CASP8 protein, human (EC 3.4.22.-) ; CASP9 protein, human (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-) ; Caspase 9 (EC 3.4.22.-) ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2004-12-02
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2004-07-2716
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 364: Show issues

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