15 results on '"Blommaert E"'
Search Results
2. Aspirations and sex: Coming of age in western Kenya in a context of HIV
- Author
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Blommaert, E., Hardon, Anita, de Bruijn, M.E., Buvé, A., and Anthropology of Health, Care and the Body (AISSR, FMG)
- Abstract
This dissertation is rooted in the daily life worlds of young people between the ages of 16 and 25 in a rural area of western Kenya (called ‘Winam’). It seeks to draw our attention to young people’s hopes, aspirations, and expectations, and shows how these young people creatively construct their daily lives in a context where HIV/AIDS has taken a toll on human lives and livelihoods. I examine the livelihood opportunities and challenges of the young people of Winam with the goal of understanding their sexual relationships and networks. More precisely, this dissertation examines how they form sexual relationships, avoid the health risks associated with sex, and understand the links between sex, love, and money. I argue that young people’s aspirations and concerns need to be examined through a lens of intergenerational relations (see Cole and Durham 2007). Young people’s perceptions of a ‘state-of-the-art’ HIV/AIDS prevention project are also analysed in order to discern the role such interventions play in their daily lives.
- Published
- 2014
3. The Dust Sequence along the AGB
- Author
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A. D. L. Blommaert E. Vanhollebeke J. Cami M. A. T. Groenewegen H. J. Habing F. Markwick-Kember A. Omont M. Schultheis A. G. G. M. Tielens L. B. F. M. Waters P. R. Wood, J., Institut Bisontin en Sciences Fondamentales (IBSF), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), F. Kerschbaum, C. Charbonnel et & R. F. Wing, eds, Debray, Bernard, and F. Kerschbaum, C. Charbonnel et & R. F. Wing, eds
- Subjects
ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2007
4. Evidence of xylitol effects on salivary Streptococcus mutans and Lactobacillus.
- Author
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UCL - MD/MDEN - Ecole de médecine dentaire et de stomatologie, UCL - MD/ESP - Ecole de santé publique, Leloup, Gaëtane, D'Hoore, William, Blommaert, E, Vreven, José, UCL - MD/MDEN - Ecole de médecine dentaire et de stomatologie, UCL - MD/ESP - Ecole de santé publique, Leloup, Gaëtane, D'Hoore, William, Blommaert, E, and Vreven, José
- Published
- 2001
5. Plasma and Specific Protein Excretion Rates as Evdence of Differential Renal Dysfunctions during Short- and Medium-Term Exercises in Men
- Author
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Poortmans, JR, primary, Blommaert, E, additional, Baptisa, M, additional, Brasseur, M, additional, Leclercq, R, additional, De Broe, ME, additional, and Nouwen, EJ, additional
- Published
- 1994
- Full Text
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6. Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function
- Author
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Mireia Tena-Garitaonaindia, Berta Sáez, Wonji Kim, Álvaro Casanova, Coline H.M. van Moorsel, José Antonio Rodríguez-Portal, Rosalía Laporta, Eline Blommaert, Krinio Giannikou, Julio Ancochea, Antonio Roman, Fermín Sánchez de Medina, Miquel Angel Pujana, Rafael de Cid, Maria Molina-Molina, Carmen Herranz, Piedad Ussetti, Claudia Valenzuela, Francesca Mateo, Roderic Espín, Alexandra Baiges, Marian J.R. Quanjel, Xavier Farré, David J. Kwiatkowski, Sungho Won, Joanne J. van der Vis, Institut Català de la Salut, [Farré X] Genomes for Life – GCAT Lab Group, Institut Germans Trias i Pujol, Badalona, Spain. [Espín R, Baiges A, Blommaert E] ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, Spain. [Kim W] Channing Division of Network Medicine, Dept of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA. [Giannikou K] Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Román A, Sáez B] Unitat de Trasplantament Pulmonar, Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Asociación Española de Linfangioleiomiomatosis, LAM Foundation, Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, and Institut Germans Trias i Pujol
- Subjects
Pulmonary and Respiratory Medicine ,Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Bioinformatics ,Interstitial Lung Disease ,Pulmonary function testing ,Interstitial and orphan lung disease ,Lung structure and function ,Genòmica comparativa ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Genetics ,Original Research Article ,Genetic risk ,neoplasias::neoplasias por tipo histológico::tumores de los vasos linfáticos::linfangiomioma::linfangioleiomiomatosis [ENFERMEDADES] ,business.industry ,bacterial infections and mycoses ,medicine.disease ,Pulmons - Malalties ,Respiratory Tract Diseases::Lung Diseases [DISEASES] ,Lymphangioleiomyomatosis ,técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::estudio de asociación genómica completa [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,lipids (amino acids, peptides, and proteins) ,Neoplasms::Neoplasms by Histologic Type::Lymphatic Vessel Tumors::Lymphangiomyoma::Lymphangioleiomyomatosis [DISEASES] ,enfermedades respiratorias::enfermedades pulmonares [ENFERMEDADES] ,business - Abstract
This research was supported by Asociacion Espanola de LAM; The LAM Foundation Seed Grant 2019; Carlos III Institute of Health grants PI18/01029, PI21/01306 and ICI19/00047 (co-funded by European Regional Development Fund (ERDF), "A way to build Europe"); Ministry of Economy and Competitivity grant SAF2017-88457-R; the Generalitat de Catalunya SGR 2017-449 and 2017-529; PERIS PFI-Salut SLT017-20-000076; and the CERCA Program to IDIBELL and Institut Germans Trias i Pujol. X. Farre is supported by the VEIS project (001-P-001647, ERDF Operational Programme of Catalonia 2014-2020; co-funded by ERDF, "A way to build Europe"). Funding information for this article has been deposited with the Crossref Funder Registry., Introduction Lymphangioleiomyomatosis (LAM) is a rare low-grade metastasising disease characterised by cystic lung destruction. The genetic basis of LAM remains incompletely determined, and the disease cell-of-origin is uncertain. We analysed the possibility of a shared genetic basis between LAM and cancer, and LAM and pulmonary function. Methods The results of genome-wide association studies of LAM, 17 cancer types and spirometry measures (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and peak expiratory flow (PEF)) were analysed for genetic correlations, shared genetic variants and causality. Genomic and transcriptomic data were examined, and immunodetection assays were performed to evaluate pleiotropic genes. Results There were no significant overall genetic correlations between LAM and cancer, but LAM correlated negatively with FVC and PEF, and a trend in the same direction was observed for FEV1. 22 shared genetic variants were uncovered between LAM and pulmonary function, while seven shared variants were identified between LAM and cancer. The LAM-pulmonary function shared genetics identified four pleiotropic genes previously recognised in LAM single-cell transcriptomes: ADAM12, BNC2, NR2F2 and SP5. We had previously associated NR2F2 variants with LAM, and we identified its functional partner NR3C1 as another pleotropic factor. NR3C1 expression was confirmed in LAM lung lesions. Another candidate pleiotropic factor, CNTN2, was found more abundant in plasma of LAM patients than that of healthy women. Conclusions This study suggests the existence of a common genetic aetiology between LAM and pulmonary function., Asociacion Espanola de LAM, LAM Foundation Seed Grant 2019, Instituto de Salud Carlos III PI18/01029 PI21/01306 ICI19/00047, European Regional Development Fund (ERDF), "A way to build Europe", Ministry of Economy and Competitivity SAF2017-88457-R, Generalitat de Catalunya, General Electric SGR 2017-449 2017-529, PERIS PFI-Salut SLT017-20-000076, CERCA Program, VEIS project 001-P-001647, ERDF, "A way to build Europe" ERDF Operational Programme of Catalonia 2014-2020
- Published
- 2022
7. Lack of NKG2D in MAGT1-deficient patients is caused by hypoglycosylation.
- Author
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Blommaert E, Cherepanova NA, Staels F, Wilson MP, Gilmore R, Schrijvers R, Jaeken J, Foulquier F, and Matthijs G
- Subjects
- Humans, Magnesium metabolism, NK Cell Lectin-Like Receptor Subfamily K genetics, NK Cell Lectin-Like Receptor Subfamily K metabolism, Cation Transport Proteins genetics, Cation Transport Proteins metabolism, Immunologic Deficiency Syndromes, Lymphoproliferative Disorders, X-Linked Combined Immunodeficiency Diseases genetics
- Abstract
Mutations in the X-linked gene MAGT1 cause a Congenital Disorder of Glycosylation (CDG), with two distinct clinical phenotypes: a primary immunodeficiency (XMEN disorder) versus intellectual and developmental disability. It was previously established that MAGT1 deficiency abolishes steady-state expression of the immune response protein NKG2D (encoded by KLRK1) in lymphocytes. Here, we show that the reduced steady-state levels of NKG2D are caused by hypoglycosylation of the protein and we pinpoint the exact site that is underglycosylated in MAGT1-deficient patients. Furthermore, we challenge the possibility that supplementation with magnesium restores NKG2D levels and show that the addition of this ion does not significantly improve NKG2D steady-state expression nor does it rescue the hypoglycosylation defect in CRISPR-engineered human cell lines. Moreover, magnesium supplementation of an XMEN patient did not result in restoration of NKG2D expression on the cell surface of lymphocytes. In summary, we demonstrate that in MAGT1-deficient patients, the lack of NKG2D is caused by hypoglycosylation, further elucidating the pathophysiology of XMEN/MAGT1-CDG., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
- Full Text
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8. Modification of BRCA1-associated breast cancer risk by HMMR overexpression.
- Author
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Mateo F, He Z, Mei L, de Garibay GR, Herranz C, García N, Lorentzian A, Baiges A, Blommaert E, Gómez A, Mirallas O, Garrido-Utrilla A, Palomero L, Espín R, Extremera AI, Soler-Monsó MT, Petit A, Li R, Brunet J, Chen K, Tan S, Eaves CJ, McCloskey C, Hakem R, Khokha R, Lange PF, Lázaro C, Maxwell CA, and Pujana MA
- Subjects
- Actin-Related Protein 2-3 Complex genetics, Animals, Carcinogenesis genetics, Female, Genome-Wide Association Study, Heterozygote, Humans, Mice, Tumor Microenvironment genetics, BRCA1 Protein genetics, Breast Neoplasms pathology, Extracellular Matrix Proteins genetics, Hyaluronan Receptors genetics
- Abstract
Breast cancer risk for carriers of BRCA1 pathological variants is modified by genetic factors. Genetic variation in HMMR may contribute to this effect. However, the impact of risk modifiers on cancer biology remains undetermined and the biological basis of increased risk is poorly understood. Here, we depict an interplay of molecular, cellular, and tissue microenvironment alterations that increase BRCA1-associated breast cancer risk. Analysis of genome-wide association results suggests that diverse biological processes, including links to BRCA1-HMMR profiles, influence risk. HMMR overexpression in mouse mammary epithelium increases Brca1-mutant tumorigenesis by modulating the cancer cell phenotype and tumor microenvironment. Elevated HMMR activates AURKA and reduces ARPC2 localization in the mitotic cell cortex, which is correlated with micronucleation and activation of cGAS-STING and non-canonical NF-κB signaling. The initial tumorigenic events are genomic instability, epithelial-to-mesenchymal transition, and tissue infiltration of tumor-associated macrophages. The findings reveal a biological foundation for increased risk of BRCA1-associated breast cancer., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
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9. Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function.
- Author
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Farré X, Espín R, Baiges A, Blommaert E, Kim W, Giannikou K, Herranz C, Román A, Sáez B, Casanova Á, Ancochea J, Valenzuela C, Ussetti P, Laporta R, Rodríguez-Portal JA, van Moorsel CHM, van der Vis JJ, Quanjel MJR, Tena-Garitaonaindia M, Sánchez de Medina F, Mateo F, Molina-Molina M, Won S, Kwiatkowski DJ, de Cid R, and Pujana MA
- Abstract
Introduction: Lymphangioleiomyomatosis (LAM) is a rare low-grade metastasising disease characterised by cystic lung destruction. The genetic basis of LAM remains incompletely determined, and the disease cell-of-origin is uncertain. We analysed the possibility of a shared genetic basis between LAM and cancer, and LAM and pulmonary function., Methods: The results of genome-wide association studies of LAM, 17 cancer types and spirometry measures (forced expiratory volume in 1 s (FEV
1 ), forced vital capacity (FVC), FEV1 /FVC ratio and peak expiratory flow (PEF)) were analysed for genetic correlations, shared genetic variants and causality. Genomic and transcriptomic data were examined, and immunodetection assays were performed to evaluate pleiotropic genes., Results: There were no significant overall genetic correlations between LAM and cancer, but LAM correlated negatively with FVC and PEF, and a trend in the same direction was observed for FEV1 . 22 shared genetic variants were uncovered between LAM and pulmonary function, while seven shared variants were identified between LAM and cancer. The LAM-pulmonary function shared genetics identified four pleiotropic genes previously recognised in LAM single-cell transcriptomes: ADAM12 , BNC2 , NR2F2 and SP5 . We had previously associated NR2F2 variants with LAM, and we identified its functional partner NR3C1 as another pleotropic factor. NR3C1 expression was confirmed in LAM lung lesions. Another candidate pleiotropic factor, CNTN2, was found more abundant in plasma of LAM patients than that of healthy women., Conclusions: This study suggests the existence of a common genetic aetiology between LAM and pulmonary function., Competing Interests: Conflict of interest: X. Farré has nothing to disclose. Conflict of interest: R. Espín has nothing to disclose. Conflict of interest: A. Baiges has nothing to disclose. Conflict of interest: E. Blommaert has nothing to disclose. Conflict of interest: W. Kim has nothing to disclose. Conflict of interest: K. Giannikou has nothing to disclose. Conflict of interest: C. Herranz has nothing to disclose. Conflict of interest: A. Román has nothing to disclose. Conflict of interest: B. Sáez has nothing to disclose. Conflict of interest: Á. Casanova has nothing to disclose. Conflict of interest: J. Ancochea has nothing to disclose. Conflict of interest: C. Valenzuela has nothing to disclose. Conflict of interest: P. Ussetti has nothing to disclose. Conflict of interest: R. Laporta has nothing to disclose. Conflict of interest: J.A. Rodríguez-Portal has nothing to disclose. Conflict of interest: C.H.M. van Moorsel has nothing to disclose. Conflict of interest: J.J. van der Vis has nothing to disclose. Conflict of interest: M.J.R. Quanjel has nothing to disclose. Conflict of interest: M. Tena-Garitaonaindia has nothing to disclose. Conflict of interest: F. Sánchez de Medina has nothing to disclose. Conflict of interest: F. Mateo has nothing to disclose. Conflict of interest: M. Molina-Molina has nothing to disclose. Conflict of interest: S. Won has nothing to disclose. Conflict of interest: D.J. Kwiatkowski has nothing to disclose. Conflict of interest: R. de Cid has nothing to disclose. Conflict of interest: M.A. Pujana has nothing to disclose. Support statement: This research was supported by Asociación Española de LAM; The LAM Foundation Seed Grant 2019; Carlos III Institute of Health grants PI18/01029, PI21/01306 and ICI19/00047 (co-funded by European Regional Development Fund (ERDF), “A way to build Europe”); Ministry of Economy and Competitivity grant SAF2017-88457-R; the Generalitat de Catalunya SGR 2017-449 and 2017-529; PERIS PFI-Salut SLT017-20-000076; and the CERCA Program to IDIBELL and Institut Germans Trias i Pujol. X. Farré is supported by the VEIS project (001-P-001647, ERDF Operational Programme of Catalonia 2014–2020; co-funded by ERDF, “A way to build Europe”). Funding information for this article has been deposited with the Crossref Funder Registry., (Copyright ©The authors 2022.)- Published
- 2022
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10. Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion.
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Sun X, Wu B, Chiang HC, Deng H, Zhang X, Xiong W, Liu J, Rozeboom AM, Harris BT, Blommaert E, Gomez A, Garcia RE, Zhou Y, Mitra P, Prevost M, Zhang D, Banik D, Isaacs C, Berry D, Lai C, Chaldekas K, Latham PS, Brantner CA, Popratiloff A, Jin VX, Zhang N, Hu Y, Pujana MA, Curiel TJ, An Z, and Li R
- Subjects
- Animals, Cell Line, Tumor, Discoidin Domain Receptor 1 antagonists & inhibitors, Discoidin Domain Receptor 1 deficiency, Discoidin Domain Receptor 1 genetics, Disease Models, Animal, Extracellular Matrix immunology, Female, Gene Deletion, Gene Knockout Techniques, Humans, Immunocompetence immunology, Immunotherapy, Mice, T-Lymphocytes cytology, T-Lymphocytes immunology, Triple Negative Breast Neoplasms therapy, Collagen metabolism, Discoidin Domain Receptor 1 metabolism, Extracellular Matrix metabolism, Triple Negative Breast Neoplasms immunology, Triple Negative Breast Neoplasms metabolism, Tumor Escape
- Abstract
Immune exclusion predicts poor patient outcomes in multiple malignancies, including triple-negative breast cancer (TNBC)
1 . The extracellular matrix (ECM) contributes to immune exclusion2 . However, strategies to reduce ECM abundance are largely ineffective or generate undesired outcomes3,4 . Here we show that discoidin domain receptor 1 (DDR1), a collagen receptor with tyrosine kinase activity5 , instigates immune exclusion by promoting collagen fibre alignment. Ablation of Ddr1 in tumours promotes the intratumoral penetration of T cells and obliterates tumour growth in mouse models of TNBC. Supporting this finding, in human TNBC the expression of DDR1 negatively correlates with the intratumoral abundance of anti-tumour T cells. The DDR1 extracellular domain (DDR1-ECD), but not its intracellular kinase domain, is required for immune exclusion. Membrane-untethered DDR1-ECD is sufficient to rescue the growth of Ddr1-knockout tumours in immunocompetent hosts. Mechanistically, the binding of DDR1-ECD to collagen enforces aligned collagen fibres and obstructs immune infiltration. ECD-neutralizing antibodies disrupt collagen fibre alignment, mitigate immune exclusion and inhibit tumour growth in immunocompetent hosts. Together, our findings identify a mechanism for immune exclusion and suggest an immunotherapeutic target for increasing immune accessibility through reconfiguration of the tumour ECM., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
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11. Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue.
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Espín R, Baiges A, Blommaert E, Herranz C, Roman A, Saez B, Ancochea J, Valenzuela C, Ussetti P, Laporta R, Rodríguez-Portal JA, van Moorsel CHM, van der Vis JJ, Quanjel MJR, Villar-Piqué A, Diaz-Lucena D, Llorens F, Casanova Á, Molina-Molina M, Plass M, Mateo F, Moss J, and Pujana MA
- Subjects
- Female, Humans, Biomarkers, Tumor metabolism, Lymphangioleiomyomatosis genetics, Transcriptome genetics
- Abstract
Lymphangioleiomyomatosis (LAM) is a rare, low-grade metastasizing disease characterized by cystic lung destruction. LAM can exhibit extensive heterogeneity at the molecular, cellular, and tissue levels. However, the molecular similarities and differences among LAM cells and tissue, and their connection to cancer features are not fully understood. By integrating complementary gene and protein LAM signatures, and single-cell and bulk tissue transcriptome profiles, we show sources of disease heterogeneity, and how they correspond to cancer molecular portraits. Subsets of LAM diseased cells differ with respect to gene expression profiles related to hormones, metabolism, proliferation, and stemness. Phenotypic diseased cell differences are identified by evaluating lumican (LUM) proteoglycan and YB1 transcription factor expression in LAM lung lesions. The RUNX1 and IRF1 transcription factors are predicted to regulate LAM cell signatures, and both regulators are expressed in LAM lung lesions, with differences between spindle-like and epithelioid LAM cells. The cancer single-cell transcriptome profiles most similar to those of LAM cells include a breast cancer mesenchymal cell model and lines derived from pleural mesotheliomas. Heterogeneity is also found in LAM lung tissue, where it is mainly determined by immune system factors. Variable expression of the multifunctional innate immunity protein LCN2 is linked to disease heterogeneity. This protein is found to be more abundant in blood plasma from LAM patients than from healthy women. IMPLICATIONS: This study identifies LAM molecular and cellular features, master regulators, cancer similarities, and potential causes of disease heterogeneity., (©2021 American Association for Cancer Research.)
- Published
- 2021
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12. Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.
- Author
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Herranz C, Mateo F, Baiges A, Ruiz de Garibay G, Junza A, Johnson SR, Miller S, García N, Capellades J, Gómez A, Vidal A, Palomero L, Espín R, Extremera AI, Blommaert E, Revilla-López E, Saez B, Gómez-Ollés S, Ancochea J, Valenzuela C, Alonso T, Ussetti P, Laporta R, Xaubet A, Rodríguez-Portal JA, Montes-Worboys A, Machahua C, Bordas J, Menendez JA, Cruzado JM, Guiteras R, Bontoux C, La Motta C, Noguera-Castells A, Mancino M, Lastra E, Rigo-Bonnin R, Perales JC, Viñals F, Lahiguera A, Zhang X, Cuadras D, van Moorsel CHM, van der Vis JJ, Quanjel MJR, Filippakis H, Hakem R, Gorrini C, Ferrer M, Ugun-Klusek A, Billett E, Radzikowska E, Casanova Á, Molina-Molina M, Roman A, Yanes O, and Pujana MA
- Subjects
- Biomarkers, Histamine, Humans, Signal Transduction, Lung Neoplasms drug therapy, Lymphangioleiomyomatosis drug therapy
- Abstract
Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2021
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13. Immune Cell Associations with Cancer Risk.
- Author
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Palomero L, Galván-Femenía I, de Cid R, Espín R, Barnes DR, Cimba, Blommaert E, Gil-Gil M, Falo C, Stradella A, Ouchi D, Roso-Llorach A, Violan C, Peña-Chilet M, Dopazo J, Extremera AI, García-Valero M, Herranz C, Mateo F, Mereu E, Beesley J, Chenevix-Trench G, Roux C, Mak T, Brunet J, Hakem R, Gorrini C, Antoniou AC, Lázaro C, and Pujana MA
- Abstract
Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features. Polygenic risk scores also reveal associations with immune and/or stromal cell contents, and breast cancer scores show consistent results in normal and tumor tissue. SH2B3 links peripheral alterations of several immune cell types to the risk of this malignancy. Pleiotropic SH2B3 variants are associated with breast cancer risk in BRCA1/2 mutation carriers. A retrospective case-cohort study indicates a positive association between blood counts of basophils, leukocytes, and monocytes and age at breast cancer diagnosis. These findings broaden our knowledge of the role of the immune system in cancer and highlight promising prevention strategies for individuals at high risk., Competing Interests: Declaration of Interests M.A.P. is recipient of an unrestricted research grant from Roche Pharma for the development of the ProCURE ICO research program. C.F. received support from Pfizer unrelated to this study., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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14. Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype.
- Author
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Blommaert E, Péanne R, Cherepanova NA, Rymen D, Staels F, Jaeken J, Race V, Keldermans L, Souche E, Corveleyn A, Sparkes R, Bhattacharya K, Devalck C, Schrijvers R, Foulquier F, Gilmore R, and Matthijs G
- Subjects
- Adolescent, Child, Congenital Disorders of Glycosylation metabolism, DNA Mutational Analysis, Hexosyltransferases metabolism, Humans, Male, Membrane Proteins metabolism, Tumor Suppressor Proteins metabolism, Cation Transport Proteins genetics, Congenital Disorders of Glycosylation genetics
- Abstract
Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. We identified two patients with defective serum transferrin glycosylation and mutations in the MAGT1 gene. These patients present with a phenotype that is mainly characterized by intellectual and developmental disability. MAGT1 has been described to be a subunit of the oligosaccharyltransferase (OST) complex and more specifically of the STT3B complex. However, it was also claimed that MAGT1 is a magnesium (Mg
2+ ) transporter. So far, patients with mutations in MAGT1 were linked to a primary immunodeficiency, characterized by chronic EBV infections attributed to a Mg2+ homeostasis defect (XMEN). We compared the clinical and cellular phenotype of our two patients to that of an XMEN patient that we recently identified. All three patients have an N -glycosylation defect, as was shown by the study of different substrates, such as GLUT1 and SHBG, demonstrating that the posttranslational glycosylation carried out by the STT3B complex is dysfunctional in all three patients. Moreover, MAGT1 deficiency is associated with an enhanced expression of TUSC3, the homolog protein of MAGT1, pointing toward a compensatory mechanism. Hence, we delineate MAGT1-CDG as a disorder associated with two different clinical phenotypes caused by defects in glycosylation., Competing Interests: The authors declare no conflict of interest.- Published
- 2019
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15. Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.
- Author
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Gerits E, Blommaert E, Lippell A, O'Neill AJ, Weytjens B, De Maeyer D, Fierro AC, Marchal K, Marchand A, Chaltin P, Spincemaille P, De Brucker K, Thevissen K, Cammue BP, Swings T, Liebens V, Fauvart M, Verstraeten N, and Michiels J
- Subjects
- Anti-Bacterial Agents chemistry, Bacterial Proteins metabolism, Biosynthetic Pathways drug effects, Carbazoles chemistry, Carbazoles pharmacology, Cell Division drug effects, Cell Membrane drug effects, Cell Membrane metabolism, Cell Membrane Permeability drug effects, Drug Resistance, Bacterial drug effects, Fatty Acids biosynthesis, Gene Expression Profiling, Gene Regulatory Networks drug effects, Genes, Bacterial, Kinetics, Lipid Metabolism drug effects, Lipid Metabolism genetics, Liposomes chemistry, Macromolecular Substances metabolism, Microbial Sensitivity Tests, Microbial Viability drug effects, Mutation genetics, Phospholipids metabolism, Pseudomonas aeruginosa genetics, Sequence Analysis, DNA, Staphylococcus aureus genetics, Time Factors, Anti-Bacterial Agents pharmacology, Pseudomonas aeruginosa drug effects, Staphylococcus aureus drug effects
- Abstract
Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies.
- Published
- 2016
- Full Text
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