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  1. Article ; Online: Epithelial-mesenchymal transitions: from cell plasticity to concept elasticity.

    Savagner, Pierre

    Current topics in developmental biology

    2015  Volume 112, Page(s) 273–300

    Abstract: Epithelial-mesenchymal transition (EMT) is a developmental cellular process occurring during early embryo development, including gastrulation and neural crest cell migration. It can be broken down in distinct functional steps: (1) loss of baso-apical ... ...

    Abstract Epithelial-mesenchymal transition (EMT) is a developmental cellular process occurring during early embryo development, including gastrulation and neural crest cell migration. It can be broken down in distinct functional steps: (1) loss of baso-apical polarization characterized by cytoskeleton, tight junctions, and hemidesmosomes remodeling; (2) individualization of cells, including a decrease in cell-cell adhesion forces, (3) emergence of motility, and (4) invasive properties, including passing through the subepithelial basement membrane. These phases occur in an uninterrupted process, without requiring mitosis, in an order and with a degree of completion dictated by the microenvironment. The whole process reflects the activation of specific transcription factor families, called EMT transcription factors. Several mechanisms can combine to induce EMT. Some are reversible, involving growth factors and cytokines and/or environmental signals including extracellular matrix and local physical conditions. Others are irreversible, such as genomic alterations during carcinoma progression, along a selective and irreversible clonal drift. In carcinomas, these signals can converge to initiate a metastable phenotype. In this state, similarly to activated keratinocytes during re-epithelialization, cells can initiate a cohort migration and engage into a transient and reversible EMT controlled by the local environment prior to efficient intravasation and metastasis. EMT transcription factors also participate in cancer progression by inducing apoptosis resistance and maintaining stem-like properties exposed in tumor recurrences. These properties, very important on a clinical point of view, are not intrinsically linked to EMT, but can share common pathways.
    MeSH term(s) Animals ; Cell Adhesion/physiology ; Cell Movement/physiology ; Cell Plasticity/physiology ; Disease Progression ; Elasticity ; Epithelial-Mesenchymal Transition ; Humans ; Neoplasms/etiology ; Neoplasms/pathology ; Signal Transduction
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1557-8933 ; 0070-2153
    ISSN (online) 1557-8933
    ISSN 0070-2153
    DOI 10.1016/bs.ctdb.2014.11.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Twenty years of EMT: A state of the field from TEMTIA X.

    Savagner, Pierre / Brabletz, Thomas / Cheng, Chonghui / Gilles, Christine / Hong, Tian / Polette, Myriam / Sheng, Guojun / Stemmler, Marc P / Thompson, Erik W

    Cells, tissues, organs

    2024  

    Abstract: TEMTIA X, the tenth symposium organized by the EMT international Association (TEMTIA) took place in Paris on November 7th-10th, 2022. Similarly to the previous meetings, it reviewed most recent aspects of the epithelial-mesenchymal transition, a cellular ...

    Abstract TEMTIA X, the tenth symposium organized by the EMT international Association (TEMTIA) took place in Paris on November 7th-10th, 2022. Similarly to the previous meetings, it reviewed most recent aspects of the epithelial-mesenchymal transition, a cellular process involved during distinct stages of development, but also during wound healing and fibrosis to some level. EMT steps are likewise typically described with various extents during tumor cell progression and metastasis. The meeting emphasized the intermediate stages involved in the process and their potential physiological or pathological importance, taking advantage of the expansion of molecular methods at single cell level. It also introduced new descriptions of EMT occurrences during early embryogenesis. In addition, sessions explored how EMT reflects cell metabolism and how the process can mingle with immune response, particularly during tumor progression, providing new targets, that were discussed, among others, for cancer therapy. Finally, it introduced a new perception of EMT biological meaning based on an evolutionary perspective. The meeting integrated the TEMTIA general assembly , allowing general discussion about the future of the association, starting with the site of the next meeting, now decided to take place in Seattle (US), late 2024.
    Language English
    Publishing date 2024-01-09
    Publishing country Switzerland
    Document type Letter
    ZDB-ID 1468141-9
    ISSN 1422-6421 ; 1422-6405
    ISSN (online) 1422-6421
    ISSN 1422-6405
    DOI 10.1159/000536096
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Inherited Selenocysteine Transfer RNA Mutation: Clinical and Hormonal Evaluation of 2 Patients.

    Geslot, Aurore / Savagner, Frédérique / Caron, Philippe

    European thyroid journal

    2021  Volume 10, Issue 6, Page(s) 542–547

    Abstract: Introduction: Iodothyronine deiodinases are selenoproteins with the amino acid selenocysteine (Sec) introduced into the position of a TGA stop codon by a complex machinery involving tRNA: Case presentation: A 13-year-old patient was seen for ... ...

    Abstract Introduction: Iodothyronine deiodinases are selenoproteins with the amino acid selenocysteine (Sec) introduced into the position of a TGA stop codon by a complex machinery involving tRNA
    Case presentation: A 13-year-old patient was seen for Hashimoto's disease with high FT3 (4.6 pg/mL, normal range 2-4.2 pg/mL) and normal FT4 and TSH concentrations. He had no clinical complaints. During a 6-year clinical and hormonal follow-up, the index patient was not treated, FT3 decreased, FT4 increased, and serum TSH stayed in the normal range resulting in a euthyroid hyperthyroxinemia. Reverse T3 concentration was significantly increased at the last visit (19 years and 4 months). At the last evaluation, the total selenium level was low (91 μg/L, normal range 95-125). DNA sequencing identified a germinal homozygous variant (C65G) in the
    Discussion/conclusion: We report on 2 members of a family with a variant in the
    Language English
    Publishing date 2021-08-26
    Publishing country England
    Document type Case Reports
    ZDB-ID 2659767-6
    ISSN 2235-0802 ; 2235-0640
    ISSN (online) 2235-0802
    ISSN 2235-0640
    DOI 10.1159/000518275
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Epithelial-mesenchymal transition and plasticity in the developmental basis of cancer and fibrosis.

    Runyan, Raymond B / Savagner, Pierre

    Developmental dynamics : an official publication of the American Association of Anatomists

    2018  Volume 247, Issue 3, Page(s) 330–331

    MeSH term(s) Epithelial-Mesenchymal Transition ; Fibrosis/etiology ; Fibrosis/pathology ; Humans ; Neoplasms/etiology ; Neoplasms/pathology
    Language English
    Publishing date 2018-02-14
    Publishing country United States
    Document type Editorial
    ZDB-ID 1102541-4
    ISSN 1097-0177 ; 1058-8388
    ISSN (online) 1097-0177
    ISSN 1058-8388
    DOI 10.1002/dvdy.24620
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The epithelial-mesenchymal transition (EMT) phenomenon.

    Savagner, P

    Annals of oncology : official journal of the European Society for Medical Oncology

    2010  Volume 21 Suppl 7, Page(s) vii89–92

    Abstract: The epithelial-mesenchymal transition (EMT) describes a rapid and often reversible modulation of phenotype by epithelial cells. EMT was originally defined in the context of developmental stages, including heart morphogenesis, mesoderm and neural crest ... ...

    Abstract The epithelial-mesenchymal transition (EMT) describes a rapid and often reversible modulation of phenotype by epithelial cells. EMT was originally defined in the context of developmental stages, including heart morphogenesis, mesoderm and neural crest formation. Epithelial cells loosen cell-cell adhesion structures throughout EMT. They modulate their polarity, cytoskeleton organization and typically express vimentin filaments and downregulate cytokeratins. They become isolated, mobile and resistant to anoikis. The EMT at least superficially resembles the evolution from normal to transformed cell phenotype during carcinoma progression. The relevance of the concept of EMT in this context was indicated by in vitro models using transformed epithelial cells. Transduction pathways typical of embryogenic EMT in vivo were also found to be activated during cancer progression. More recently, it has been found that such pathways indicate an increased plasticity linked to cellular stemness and ability to generate tumors. However, in the absence of direct evidence, a number of oncologists and pathologists remain skeptical about applying the EMT concept to human tumor progression. Typically in the cancer field, EMT concept appears to be fully relevant in some situations, but the concept has to be adjusted in other situations to reflect tumor cell renewal and plasticity during carcinoma progression and metastasis.
    MeSH term(s) Animals ; Cell Dedifferentiation/physiology ; Epithelial-Mesenchymal Transition/physiology ; Female ; Humans ; Mammary Neoplasms, Experimental/pathology ; Mice ; Neoplasms/etiology ; Neoplasms/pathology
    Language English
    Publishing date 2010-10-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1025984-3
    ISSN 1569-8041 ; 0923-7534
    ISSN (online) 1569-8041
    ISSN 0923-7534
    DOI 10.1093/annonc/mdq292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Evaluating immune response

    Doffe, Flora / Fuoco, Layla / Michels, Judith / Jernström, Sandra / Tomasi, Raphael / Savagner, Pierre

    Exploration of targeted anti-tumor therapy

    2022  Volume 3, Issue 6, Page(s) 853–865

    Abstract: Aim: Functional screening of new pharmaceutical compounds requires clinically relevant models to monitor essential cellular and immune responses during cancer progression, with or without treatment. Beyond survival, the emergence of resistant tumor cell ...

    Abstract Aim: Functional screening of new pharmaceutical compounds requires clinically relevant models to monitor essential cellular and immune responses during cancer progression, with or without treatment. Beyond survival, the emergence of resistant tumor cell clones should also be considered, including specific properties related to plasticity, such as invasiveness, stemness, escape from programmed cell death, and immune response. Numerous pathways are involved in these processes. Defining the relevant ones in the context of a specific tumor type will be key to designing an appropriate combination of inhibitors. However, the diversity and potential redundancy of these pathways remain a challenge for therapy.
    Methods: A new microfluidic device developed by Okomera was dedicated to the screening of drug treatment for breast cancer. This microchip includes 150 droplet-trapping microwells, offering multi-chip settings and multiple treatment choices.
    Results: After validating the system with established cell lines and a panel of drugs used clinically at Gustave Roussy, preclinical experiments were initiated including patient-derived xenograft (PDX) and primary tumor cells-derived tumoroids with the collaboration of Gustave Roussy clinicians. Tumor-isolated lymphocytes were also added to the tumoroids, using secondary droplets in proof-of-concept experiments.
    Conclusions: These results show the relevance of the methodology for screening large numbers of drugs, a wide range of doses, and multiple drug combinations. This methodology will be used for two purposes: 1) new drug screening from the compound library, using the high throughput potential of the chip; and 2) pre-clinical assay for a two-weeks response for personalized medicine, allowing evaluation of drug combinations to flag an optimized treatment with potential clinical application.
    Language English
    Publishing date 2022-12-29
    Publishing country United States
    Document type Journal Article
    ISSN 2692-3114
    ISSN (online) 2692-3114
    DOI 10.37349/etat.2022.00117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Designing Organoid Models to Monitor Cancer Progression, Plasticity and Resistance: The Right Set Up for the Right Question.

    Doffe, Flora / Bonini, Fabien / Lakis, Emile / Terry, Stéphane / Chouaib, Salem / Savagner, Pierre

    Cancers

    2022  Volume 14, Issue 15

    Abstract: The recent trend in 3D cell modeling has fostered the emergence of a wide range of models, addressing very distinct goals ranging from the fundamental exploration of cell-cell interactions to preclinical assays for personalized medicine. It is clear that ...

    Abstract The recent trend in 3D cell modeling has fostered the emergence of a wide range of models, addressing very distinct goals ranging from the fundamental exploration of cell-cell interactions to preclinical assays for personalized medicine. It is clear that no single model will recapitulate the complexity and dynamics of in vivo situations. The key is to define the critical points, achieve a specific goal and design a model where they can be validated. In this report, we focused on cancer progression. We describe our model which is designed to emulate breast carcinoma progression during the invasive phase. We chose to provide topological clues to the target cells by growing them on microsupports, favoring a polarized epithelial organization before they are embedded in a 3D matrix. We then watched for cell organization and differentiation for these models, adding stroma cells then immune cells to follow and quantify cell responses to drug treatment, including quantifying cell death and viability, as well as morphogenic and invasive properties. We used model cell lines including Comma Dβ, MCF7 and MCF10A mammary epithelial cells as well as primary breast cancer cells from patient-derived xenografts (PDX). We found that fibroblasts impacted cell response to Docetaxel and Palbociclib. We also found that NK92 immune cells could target breast cancer cells within the 3D configuration, providing quantitative monitoring of cell cytotoxicity. We also tested several sources for the extracellular matrix and selected a hyaluronan-based matrix as a promising alternative to mouse tumor basement membrane extracts for primary human cancer cells. Overall, we validated a new 3D model designed for breast cancer for preclinical use in personalized medicine.
    Language English
    Publishing date 2022-07-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14153559
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Transition épithélio-mésenchymateuse et pathologie mammaire.

    Savagner, Pierre

    Annales de pathologie

    2009  Volume 29 Spec No 1, Page(s) S61–2

    Title translation Epithelial-mesenchymal transition and breast pathology.
    MeSH term(s) Apoptosis ; Biomarkers ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Carcinoma/metabolism ; Carcinoma/pathology ; Cell Transdifferentiation ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Female ; Humans ; Mesoderm/metabolism ; Mesoderm/pathology ; Neoplasm Proteins/physiology ; Snail Family Transcription Factors ; Transcription Factors/physiology
    Chemical Substances Biomarkers ; Neoplasm Proteins ; Snail Family Transcription Factors ; Transcription Factors
    Language French
    Publishing date 2009-11
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 225720-8
    ISSN 0242-6498
    ISSN 0242-6498
    DOI 10.1016/j.annpat.2009.07.039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Transition épithélio-mésenchymateuse: le concept.

    Savagner, Pierre

    Annales de pathologie

    2009  Volume 29 Spec No 1, Page(s) S59–60

    Title translation Epithelial-mesenchymal transition: the concept.
    MeSH term(s) Biomarkers ; Cell Adhesion ; Cell Transdifferentiation/physiology ; Epithelial Cells/chemistry ; Epithelial Cells/cytology ; Epithelial Cells/pathology ; Humans ; Mesoderm/chemistry ; Mesoderm/cytology ; Mesoderm/pathology
    Chemical Substances Biomarkers
    Language French
    Publishing date 2009-11
    Publishing country France
    Document type Journal Article
    ZDB-ID 225720-8
    ISSN 0242-6498
    ISSN 0242-6498
    DOI 10.1016/j.annpat.2009.07.038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Update of the UMD-VHL database: classification of 164 challenging variants based on genotype-phenotype correlation among 605 entries.

    Mougel, Gregory / Mohamed, Amira / Burnichon, Nelly / Giraud, Sophie / Pigny, Pascal / Bressac-de Paillerets, Brigitte / Mirebeau-Prunier, Delphine / Buffet, Alexandre / Savagner, Frédérique / Romanet, Pauline / Arlot, Yannick / Gardie, Betty / Gimenez-Roqueplo, Anne-Paule / Beroud, Christophe / Richard, Stephane / Barlier, Anne

    Journal of medical genetics

    2024  Volume 61, Issue 4, Page(s) 378–384

    Abstract: Background: The von Hippel-Lindau (VHL) disease is a hereditary tumour syndrome caused by germline mutations in : Methods: The TENGEN (French oncogenetics network of neuroendocrine tumors) and PREDIR (French National Cancer Institute network for ... ...

    Abstract Background: The von Hippel-Lindau (VHL) disease is a hereditary tumour syndrome caused by germline mutations in
    Methods: The TENGEN (French oncogenetics network of neuroendocrine tumors) and PREDIR (French National Cancer Institute network for Inherited predispositions to kidney cancer) networks have collected
    Results: Here we report the expert classification of 164 variants, including all missense variants (n=124), all difficult interpretation variants (n=40) and their associated phenotypes. After initial American College of Medical Genetics classification, first-round classification was performed by the VHL expert group followed by a second round for discordant and ambiguous cases. Overall, the VHL experts modified the classification of 87 variants including 30 variants of uncertain significance that were as (likely)pathogenic variants for 19, and as likely benign for 11.
    Conclusion: Consequently, this work has allowed the diagnosis and influenced the genetic counselling of 45 VHL-suspected families and can benefit to the worldwide VHL community, through this review.
    MeSH term(s) Humans ; Von Hippel-Lindau Tumor Suppressor Protein/genetics ; Genetic Testing ; Genetic Predisposition to Disease ; von Hippel-Lindau Disease/genetics ; von Hippel-Lindau Disease/pathology ; Genetic Association Studies ; Kidney Neoplasms/genetics ; Germ-Line Mutation
    Chemical Substances Von Hippel-Lindau Tumor Suppressor Protein (EC 2.3.2.27) ; VHL protein, human (EC 6.3.2.-)
    Language English
    Publishing date 2024-03-21
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 220881-7
    ISSN 1468-6244 ; 0022-2593
    ISSN (online) 1468-6244
    ISSN 0022-2593
    DOI 10.1136/jmg-2023-109550
    Database MEDical Literature Analysis and Retrieval System OnLINE

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