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  1. Article: CAR-NK Cells: A Chimeric Hope or a Promising Therapy?

    Sabbah, Mohamad / Jondreville, Ludovic / Lacan, Claire / Norol, Francoise / Vieillard, Vincent / Roos-Weil, Damien / Nguyen, Stéphanie

    Cancers

    2022  Volume 14, Issue 15

    Abstract: Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable ... ...

    Abstract Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, limited number of available CAR cells, toxicities, and a high cost. Thanks to their powerful cytotoxic capabilities, with proven antitumor effects in both haploidentical hematopoietic stem cell transplantation and adoptive cell therapy against solid tumors and hematological malignancies, Natural Killer cells could be a promising alternative. Different sources of NK cells can be used, including cellular lines, cord blood, peripheral blood, and induced pluripotent stem cells. Their biggest advantage is the possibility of using them in an allogeneic context without major toxic side effects. However, the majority of the reports on CAR-NK cells concern preclinical or early clinical trials. Indeed, NK cells might be more difficult to engineer, and the optimization and standardization of expansion and transfection protocols need to be defined. Furthermore, their short persistence after infusion is also a major setback. However, with recent advances in manufacturing engineered CAR-NK cells exploiting their cytolytic capacities, antibody-dependent cellular cytotoxicity (ADCC), and cytokine production, "off-the-shelf" allogeneic CAR-NK cells can provide a great potential in cancer treatments.
    Language English
    Publishing date 2022-08-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14153839
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Successive relapses from donor and host cells in a patient with DEAD-box helicase 41 (DDX41)-associated myelodysplastic syndrome: The lessons to be learned.

    Hirsch, Pierre / Bories, Dominique / Chapiro, Elise / Nguyen-Khac, Florence / Benusiglio, Patrick R / Norol, Françoise / Nguyen, Stéphanie

    British journal of haematology

    2022  Volume 199, Issue 4, Page(s) 623–626

    MeSH term(s) Humans ; Myelodysplastic Syndromes ; DEAD-box RNA Helicases/genetics ; Recurrence
    Chemical Substances DEAD-box RNA Helicases (EC 3.6.4.13) ; DDX41 protein, human (EC 3.6.1.-)
    Language English
    Publishing date 2022-08-27
    Publishing country England
    Document type Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18433
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: FLAMSA-Busulfan-Melphalan as a Sequential Conditioning Regimen in HLA-Matched or Haploidentical Hematopoietic Stem Cell Transplantation for High-Risk Myeloid Diseases.

    Jondreville, Ludovic / Roos-Weil, Damien / Uzunov, Madalina / Boussen, Inès / Grenier, Adrien / Norol, Françoise / Morel, Véronique / Nguyen, Stéphanie / Souchet, Laetitia

    Transplantation and cellular therapy

    2021  Volume 27, Issue 11, Page(s) 915.e1–915.e8

    Abstract: Given the poor prognosis of relapsed/refractory myeloid malignancies, the concept of sequential conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be an effective approach. We sought to evaluate a sequential ... ...

    Abstract Given the poor prognosis of relapsed/refractory myeloid malignancies, the concept of sequential conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be an effective approach. We sought to evaluate a sequential scheme combining fludarabine, amsacrine, and cytarabine (FLAMSA) for cytoreduction, followed by reduced-intensity conditioning with busulfan and melphalan (FLAMSA-BuMel), which was designed to be suitable for both HLA-matched and haploidentical HSCT. This single-center retrospective study included 36 adult patients with high-risk myeloid malignancies who underwent allo-HSCT from HLA-matched (n = 19) or haploidentical (n = 17) donors. Along with the standard prophylaxis for graft-versus-host disease (GVHD), patients with a haploidentical donor received post-transplantation high-dose cyclophosphamide. A post-transplantation consolidation treatment with low-dose 5-azacytidine and prophylactic donor lymphocyte infusions was provided whenever possible. Thirty patients (83%) achieved complete remission on day +30. With a median follow-up of 30.0 months, the 2-year overall survival was 89% in the HLA-matched group versus 34% in the haploidentical group (P = .0018). The 2-year disease-free survival in these 2 groups was 68% and 34%, respectively (P = .013). At 2 years, the probability of relapse was 32% and 20%, respectively, and nonrelapse mortality was 0% and 58%, respectively (P = .0003). The leading cause of death was relapse in the HLA-matched group (3 of 19) and hemorrhagic events (5 of 17) in the haploidentical group, favored by significantly delayed platelet reconstitution and a severe GVHD context. These data confirm the feasibility of FLAMSA-BuMel as a sequential conditioning in allo-HSCT for high-risk myeloid malignancies. The use of bone marrow as the preferred graft source might reduce the incidence of acute GVHD and nonrelapse mortality in the haploidentical transplantation setting.
    MeSH term(s) Busulfan ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy ; Melphalan ; Neoplasm Recurrence, Local ; Retrospective Studies
    Chemical Substances Busulfan (G1LN9045DK) ; Melphalan (Q41OR9510P)
    Language English
    Publishing date 2021-07-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2021.07.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mass Cytometry: a robust platform for the comprehensive immunomonitoring of CAR-T-cell therapies.

    Corneau, Aurélien / Parizot, Christophe / Cherai, Mustapha / Todesco, Eve / Blanc, Catherine / Litvinova, Elena / Nguyen, Stéphanie / Roos-Weil, Damien / Guihot, Amélie / Norol, Francoise

    British journal of haematology

    2021  Volume 194, Issue 4, Page(s) 788–792

    MeSH term(s) Antigens, CD/analysis ; Antigens, CD/immunology ; Cytophotometry/methods ; Flow Cytometry/methods ; Humans ; Immunotherapy, Adoptive/methods ; Lymphoma, Large B-Cell, Diffuse/immunology ; Lymphoma, Large B-Cell, Diffuse/therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Receptors, Chimeric Antigen/analysis ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology
    Chemical Substances Antigens, CD ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2021-05-26
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.17551
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: CAR T-cell therapy for central nervous system lymphomas: blood and cerebrospinal fluid biology, and outcomes.

    Lacan, Claire / Caron, Jonathan / Tarantino, Nadine / Fouquet, Baptiste / Cherai, Mustapha / Parizot, Christophe / Morel, Véronique / Souchet, Laetitia / Uzunov, Madalina / Gorochov, Guy / Nguyen-Quoc, Stéphanie / Sourdeau, Elise / Vieillard, Vincent / Miyara, Makoto / Vinit, Angélique / Solorzano, Silvia / Soussain, Carole / Houillier, Caroline / Metz, Carole /
    Autran, Brigitte / Litvinova, Elena / Le Garff-Tavernier, Magali / Norol, Françoise / Roos-Weil, Damien / Choquet, Sylvan / Guihot, Amélie / Baron, Marine

    Haematologica

    2023  Volume 108, Issue 12, Page(s) 3485–3490

    MeSH term(s) Humans ; Immunotherapy, Adoptive/adverse effects ; Lymphoma, Non-Hodgkin ; Central Nervous System Neoplasms/therapy ; Central Nervous System ; Biology ; Cerebrospinal Fluid
    Language English
    Publishing date 2023-12-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2023.282875
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats.

    Frasca, Sophie / Norol, Françoise / Le Visage, Catherine / Collombet, Jean-Marc / Letourneur, Didier / Holy, Xavier / Sari Ali, Elhadi

    Journal of materials science. Materials in medicine

    2017  Volume 28, Issue 2, Page(s) 35

    Abstract: Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are ... ...

    Abstract Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are rarely achieved to evaluate the most appropriate approach in this context. Here, we aimed to compare different clinically relevant bone tissue engineering methods and evaluated the kinetic repair and the bone healing efficiency supported by mesenchymal stem cells and two different biomaterials, a new hydrogel scaffold and a commercial hydroxyapatite/tricalcium phosphate ceramic, alone or in combination.Syngeneic mesenchymal stem cells (5 × 10
    MeSH term(s) Animals ; Biocompatible Materials/chemistry ; Bone Marrow Cells/cytology ; Bone Regeneration ; Bone Resorption ; Bone Transplantation/methods ; Calcium Phosphates/chemistry ; Ceramics/chemistry ; Femur/pathology ; Hydrogels/chemistry ; Male ; Mesenchymal Stromal Cells/cytology ; Neovascularization, Pathologic ; Polysaccharides/chemistry ; Rats ; Rats, Inbred Lew ; Tissue Engineering/methods ; Tissue Scaffolds/chemistry ; X-Ray Microtomography
    Chemical Substances Biocompatible Materials ; Calcium Phosphates ; Hydrogels ; Polysaccharides ; calcium phosphate (97Z1WI3NDX)
    Language English
    Publishing date 2017-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1031752-1
    ISSN 1573-4838 ; 0957-4530
    ISSN (online) 1573-4838
    ISSN 0957-4530
    DOI 10.1007/s10856-016-5839-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long-term maintenance of beating areas.

    Hamidi, Sofiane / Letourneur, Didier / Aid-Launais, Rachida / Di Stefano, Antonio / Vainchenker, William / Norol, Françoise / Le Visage, Catherine

    Tissue engineering. Part A

    2014  Volume 20, Issue 7-8, Page(s) 1285–1294

    Abstract: Somatic stem cells require specific niches and three-dimensional scaffolds provide ways to mimic this microenvironment. Here, we studied a scaffold based on Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic ... ...

    Abstract Somatic stem cells require specific niches and three-dimensional scaffolds provide ways to mimic this microenvironment. Here, we studied a scaffold based on Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic development, to support human embryonic stem cells (hESCs) differentiation toward the cardiac lineage. A macroporous (pore 200 μm) Fucoidan scaffold was selected to support hESCs attachment and proliferation. Using a protocol based on the cardiogenic morphogen bone morphogenic protein 2 (BMP2) and transforming growth factor (TGFβ) followed by tumor necrosis factor (TNFα), an effector of cardiopoietic priming, we examined the cardiac differentiation in the scaffold compared to culture dishes and embryoid bodies (EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression of the 3 genes encoding for transcription factors marking the early step of embryonic cardiac differentiation NKX2.5 (p<0.05), MEF2C (p<0.01), and GATA4 (p<0.01), confirmed by flow cytometry analysis for MEF2C and NKX2.5. The ability of Fucoidan scaffolds to locally concentrate and slowly release TGFβ and TNFα was confirmed by Luminex technology. We also found that Fucoidan scaffolds supported the late stage of embryonic cardiac differentiation marked by a significantly higher atrial natriuretic factor (ANF) expression (p<0.001), although only rare beating areas were observed. We postulated that absence of mechanical stress in the soft hydrogel impaired sarcomere formation, as confirmed by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological staining of sarcomeric α-actinin. Nevertheless, Fucoidan scaffolds contributed to the development of thin filaments connecting beating areas through promotion of smooth muscle cells, thus enabling maintenance of beating areas for up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising biomaterial to control cardiac differentiation from hESCs that could be further combined with mechanical stress to promote sarcomere formation at terminal stages of differentiation.
    MeSH term(s) Cell Differentiation/drug effects ; Cell Line ; Cell Lineage/drug effects ; Cell Survival/drug effects ; Cellular Microenvironment/drug effects ; Embryonic Stem Cells/cytology ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Heart/drug effects ; Heart/physiology ; Humans ; Myocytes, Smooth Muscle/cytology ; Myocytes, Smooth Muscle/drug effects ; Polysaccharides/pharmacology ; Tissue Scaffolds/chemistry ; Transforming Growth Factor beta/metabolism ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Polysaccharides ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha ; fucoidan (9072-19-9)
    Language English
    Publishing date 2014-02-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2420582-5
    ISSN 1937-335X ; 1937-3341
    ISSN (online) 1937-335X
    ISSN 1937-3341
    DOI 10.1089/ten.TEA.2013.0149
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: A clinical trial combining megakaryocytes and haematopoietic stem cells to promote engraftment after autologous transplantation.

    Trebeden-Negre, Helene / Choquet, Sylvain / Tanguy, Marie-Laure / Rozenzwajg, Michelle / Azar, Nabih / Lefrère, Francois / Heshmati, Farhad / Belhocine, Ramdane / Vieillard, Vincent / Norol, Francoise

    British journal of haematology

    2017  Volume 183, Issue 1, Page(s) 139–142

    MeSH term(s) Adult ; Allografts ; Antigens, CD34/blood ; Female ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/cytology ; Humans ; Lymphoma, Non-Hodgkin/therapy ; Male ; Megakaryocytes/cytology ; Megakaryocytes/transplantation ; Middle Aged ; Recovery of Function ; Transplantation Conditioning/methods ; Transplantation, Autologous
    Chemical Substances Antigens, CD34
    Language English
    Publishing date 2017-09-10
    Publishing country England
    Document type Letter ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.14911
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  9. Article ; Online: CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network.

    Alcantara, Marion / Houillier, Caroline / Blonski, Marie / Rubio, Marie-Thérèse / Willems, Lise / Rascalou, Agathe Waultier / Le Garff-Tavernier, Magali / Maloum, Karim / Bravetti, Clotilde / Souchet, Laetitia / Roos-Weil, Damien / Morel, Véronique / Uzunov, Madalina / Metz, Carole / Dhib-Charfi, Meriem / Nguyen, Stéphanie / Shor, Natalia / Psimaras, Dimitri / Weiss, Nicolas /
    Jacque, Nathalie / Solorzano, Silvia / Gauthier, Nicolas / Le Cann, Marie / Norol, Françoise / Soussain, Carole / Choquet, Sylvain

    Blood

    2021  Volume 139, Issue 5, Page(s) 792–796

    MeSH term(s) Aged ; Central Nervous System/pathology ; Central Nervous System Neoplasms/epidemiology ; Central Nervous System Neoplasms/pathology ; Central Nervous System Neoplasms/therapy ; Cohort Studies ; Female ; France/epidemiology ; Humans ; Immunotherapy, Adoptive ; Lymphoma, Large B-Cell, Diffuse/epidemiology ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Large B-Cell, Diffuse/therapy ; Male ; Middle Aged ; Survival Analysis
    Language English
    Publishing date 2021-12-06
    Publishing country United States
    Document type Letter
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2021012932
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  10. Article ; Online: Combination of IL-2, rapamycin, DNA methyltransferase and histone deacetylase inhibitors for the expansion of human regulatory T cells.

    Miyara, Makoto / Chader, Driss / Burlion, Aude / Goldstein, Jérémie / Sterlin, Delphine / Norol, Françoise / Trebeden-Nègre, Hélène / Claër, Laetitia / Sakaguchi, Shimon / Marodon, Gilles / Amoura, Zahir / Gorochov, Guy

    Oncotarget

    2016  Volume 8, Issue 62, Page(s) 104733–104744

    Abstract: ... ...

    Abstract FOXP3
    Language English
    Publishing date 2016-07-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.10914
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