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  1. Article: Les sarcomes osseux monotones à cellules rondes/fusiformes avec translocations (hors Ewing).

    Vanhersecke, Lucile / Linck, Pierre-Antoine / Le Loarer, François

    Annales de pathologie

    2022  Volume 42, Issue 3, Page(s) 227–241

    Abstract: Round cell sarcomas represent a diagnostic challenge for pathologists due to the poorly differentiated pattern of these high-grade tumors. Their diagnosis often requires large immunohistochemical panels and the use of molecular pathology. These tumors ... ...

    Title translation Fusion-related round and spindle cell sarcomas of the bone (beyond Ewing).
    Abstract Round cell sarcomas represent a diagnostic challenge for pathologists due to the poorly differentiated pattern of these high-grade tumors. Their diagnosis often requires large immunohistochemical panels and the use of molecular pathology. These tumors are largely dominated by Ewing sarcomas, but new families are now well characterized, including in decreasing frequency order in bone, BCOR-altered sarcomas, NFATc2-rearranged sarcomas, mesenchymal chondrosarcomas and more rarely CIC-rearranged sarcomas and myoepithelial tumors. This progress report presents microscopic, immunohistochemical and molecular features of these tumors previously named by the inappropriate term "Ewing-like" sarcomas, in order to enable any pathologist to perceive the morphological features of these sarcomas, to select the immunohistochemical panel that will lead to the diagnosis and to better guide the molecular approach needed to establish the final diagnosis.
    MeSH term(s) Biomarkers, Tumor ; Bone Neoplasms/diagnosis ; Bone Neoplasms/genetics ; Bone Neoplasms/pathology ; Humans ; Oncogene Proteins, Fusion/genetics ; Sarcoma/diagnosis ; Sarcoma/genetics ; Sarcoma, Small Cell/diagnosis ; Soft Tissue Neoplasms/diagnosis ; Soft Tissue Neoplasms/genetics ; Soft Tissue Neoplasms/pathology
    Chemical Substances Biomarkers, Tumor ; Oncogene Proteins, Fusion
    Language French
    Publishing date 2022-02-22
    Publishing country France
    Document type Journal Article
    ZDB-ID 225720-8
    ISSN 0242-6498
    ISSN 0242-6498
    DOI 10.1016/j.annpat.2022.01.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: PRAME immunohistochemistry in soft tissue tumors and mimics: a study of 350 cases highlighting its imperfect specificity but potentially useful diagnostic applications.

    Cammareri, Chloé / Beltzung, Fanny / Michal, Michael / Vanhersecke, Lucile / Coindre, Jean-Michel / Velasco, Valérie / Le Loarer, François / Vergier, Béatrice / Perret, Raul

    Virchows Archiv : an international journal of pathology

    2023  Volume 483, Issue 2, Page(s) 145–156

    Abstract: Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge of its expression patterns in soft tissue tumors is limited. PRAME ... ...

    Abstract Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge of its expression patterns in soft tissue tumors is limited. PRAME immunohistochemistry (clone QR005) was assessed on whole tissue sections of 350 soft-tissue tumors and mimics (> 50 histotypes). PRAME immunoreactivity was evaluated as follows: 0 "negative" (0% positive cells); 1+ (1-25% positive cells); 2+ (26-50% positive cells); 3+ (51-75% positive cells), and 4+ "diffuse" (> 75% positive cells). PRAME was expressed in 111 lesions (0 benign, 6 intermediate malignancy, and 105 malignant), including fibrosarcomatous dermatofibrosarcoma protuberans (2/4, 0 diffuse), NTRK-rearranged spindle cell neoplasm (2/4, 0 diffuse), atypical fibroxanthoma (1/7, 0 diffuse), Kaposi sarcoma (1/5, 0 diffuse), myxoid liposarcoma (11/11, 9 diffuse), synovial sarcoma (11/11, 6 diffuse), intimal sarcoma (7/7, 5 diffuse), biphenotypic sinonasal sarcoma (3/3, 1 diffuse), angiosarcoma (10/15, 6 diffuse), malignant peripheral nerve sheath tumor (9/12, 4 diffuse), pleomorphic rhabdomyosarcoma (2/3, 2 diffuse), alveolar rhabdomyosarcoma (2/6, 0 diffuse), embryonal rhabdomyosarcoma (7/7, 4 diffuse), undifferentiated pleomorphic sarcoma (2/12, 1 diffuse), leiomyosarcoma (2/15, 1 diffuse), clear cell sarcoma of soft tissue (1/10, 0 diffuse), low-grade fibromyxoid sarcoma (1/5, 0 diffuse), Ewing sarcoma (2/10, 1 diffuse), CIC-rearranged sarcoma (8/8, 4 diffuse), BCOR-sarcoma (2/5, 1 diffuse), melanoma (20/20, 14 diffuse), and thoracic SMARCA4-deficient undifferentiated tumor (5/5, all diffuse). All tested cases of spindle cell lipoma, dedifferentiated/pleomorphic liposarcoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, inflammatory myofibroblastic tumor, myxoinflammatory fibroblastic sarcoma, nodular fasciitis, myxofibrosarcoma, epithelioid hemangioendothelioma, atypical vascular lesion, hemangioma, lymphangioma, vascular malformation, papillary endothelial hyperplasia, GIST, gastrointestinal clear-cell sarcoma, malignant melanotic nerve sheath tumor, neurofibroma, schwannoma, granular cell tumor, alveolar soft part sarcoma, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma, myoepithelioma, ossifying fibromyxoid tumor, angiomatoid fibrous histiocytoma, PEComa, dermatofibroma, pleomorphic dermal sarcoma, and chordoma were negative. PRAME shows imperfect specificity in soft-tissue pathology but may serve as a diagnostic adjunct in selected differential diagnoses that show contrasting expression patterns.
    MeSH term(s) Humans ; Adult ; Immunohistochemistry ; Sarcoma/diagnosis ; Sarcoma/pathology ; Soft Tissue Neoplasms/diagnosis ; Soft Tissue Neoplasms/pathology ; Sarcoma, Ewing/diagnosis ; Skin Neoplasms/pathology ; Transcription Factors ; Fibrosarcoma/diagnosis ; Melanoma/pathology ; Diagnosis, Differential ; Biomarkers, Tumor/metabolism ; DNA Helicases ; Nuclear Proteins ; Antigens, Neoplasm
    Chemical Substances Transcription Factors ; Biomarkers, Tumor ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-) ; Nuclear Proteins ; PRAME protein, human ; Antigens, Neoplasm
    Language English
    Publishing date 2023-07-21
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-023-03606-6
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  3. Article: Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study.

    Crombé, Amandine / Bertolo, Frédéric / Vanhersecke, Lucile / Guegan, Jean-Philippe / Bessede, Alban / Perret, Raul / Le Loarer, François / Chaire, Vanessa / Coindre, Jean-Michel / Lucchesi, Carlo / Italiano, Antoine

    Biomarker research

    2024  Volume 12, Issue 1, Page(s) 3

    Abstract: Metabolic elevation in soft-tissue sarcomas (STS), as documented ... ...

    Abstract Metabolic elevation in soft-tissue sarcomas (STS), as documented with
    Language English
    Publishing date 2024-01-07
    Publishing country England
    Document type Letter
    ZDB-ID 2699926-2
    ISSN 2050-7771
    ISSN 2050-7771
    DOI 10.1186/s40364-023-00552-y
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  4. Article ; Online: Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide.

    Toulmonde, Maud / Guegan, Jean-Philippe / Spalato-Ceruso, Mariella / Peyraud, Florent / Kind, Michèle / Vanhersecke, Lucile / Le Loarer, François / Perret, Raul / Cantarel, Coralie / Bellera, Carine / Bessede, Alban / Italiano, Antoine

    Molecular cancer

    2024  Volume 23, Issue 1, Page(s) 38

    Abstract: Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can ... ...

    Abstract Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, 'cold' STS, characterized by an absence of tertiary lymphoid structures. The trial employed a two-stage Simon design. JX-594 was administered intratumorally at a dose of 1.10
    MeSH term(s) Humans ; Tumor Microenvironment ; Oncolytic Virotherapy/adverse effects ; Oncolytic Viruses/genetics ; Oncolytic Viruses/metabolism ; Sarcoma/therapy ; Cyclophosphamide/therapeutic use ; Cyclophosphamide/metabolism ; Antibodies, Monoclonal, Humanized
    Chemical Substances avelumab (KXG2PJ551I) ; Cyclophosphamide (8N3DW7272P) ; Antibodies, Monoclonal, Humanized
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Clinical Trial, Phase II ; Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2091373-4
    ISSN 1476-4598 ; 1476-4598
    ISSN (online) 1476-4598
    ISSN 1476-4598
    DOI 10.1186/s12943-024-01946-8
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  5. Article ; Online: TROP2 Is Associated with Primary Resistance to Immune Checkpoint Inhibition in Patients with Advanced Non-Small Cell Lung Cancer.

    Bessede, Alban / Peyraud, Florent / Besse, Benjamin / Cousin, Sophie / Cabart, Mathilde / Chomy, François / Rey, Christophe / Lara, Oren / Odin, Ophélie / Nafia, Imane / Vanhersecke, Lucile / Barlesi, Fabrice / Guégan, Jean-Philippe / Italiano, Antoine

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

    2023  Volume 30, Issue 4, Page(s) 779–785

    Abstract: Purpose: Mechanisms of primary resistance to inhibitors of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis in non-small cell lung cancer (NSCLC) are still poorly understood. While some studies suggest the involvement ... ...

    Abstract Purpose: Mechanisms of primary resistance to inhibitors of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis in non-small cell lung cancer (NSCLC) are still poorly understood. While some studies suggest the involvement of trophoblast cell surface antigen 2 (TROP2) in modulating tumor cell resistance to therapeutic drugs, its specific role in the context of PD-1/PD-L1 axis blockade is not definitively established.
    Experimental design: We performed high-throughput analysis of transcriptomic data from 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy in two large randomized clinical trials. To confirm our results at the protein level, we complemented this transcriptional approach by performing a multiplex immunofluorescence analysis of tumor tissue samples as well as a proteomic profiling of plasma.
    Results: We observed a significant association of TROP2 overexpression with worse progression-free survival and overall survival on PD-L1 blockade, independent of other prognostic factors. Importantly, we found increased TROP2 expression to be predictive of survival in patients treated with atezolizumab but not chemotherapy. TROP2 overexpression was associated with decreased T-cell infiltration. We confirmed these results at the proteomic level both on tumor tissue and in plasma.
    Conclusions: Our results suggest an important contribution of TROP2 expression to the primary resistance to PD-L1 blockade in NSCLC. TROP2-biomarker-based strategy may be relevant in selecting patients with NSCLC who are more likely to benefit from a combination of immunotherapy and an anti-TROP2 agent.
    MeSH term(s) Humans ; B7-H1 Antigen/metabolism ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Immune Checkpoint Inhibitors/therapeutic use ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Programmed Cell Death 1 Receptor ; Proteomics
    Chemical Substances B7-H1 Antigen ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor ; TACSTD2 protein, human
    Language English
    Publishing date 2023-12-04
    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-23-2566
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    Zs.A 4223: Show issues Location:
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  6. Article ; Online: Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers.

    Vanhersecke, Lucile / Bougouin, Antoine / Crombé, Amandine / Brunet, Maxime / Sofeu, Casimir / Parrens, Marie / Pierron, Hugo / Bonhomme, Benjamin / Lembege, Nicolas / Rey, Christophe / Velasco, Valérie / Soubeyran, Isabelle / Begueret, Hugues / Bessede, Alban / Bellera, Carine / Scoazec, Jean-Yves / Italiano, Antoine / Fridman, Catherine Sautès / Fridman, Wolf H /
    Le Loarer, François

    Laboratory investigation; a journal of technical methods and pathology

    2023  Volume 103, Issue 5, Page(s) 100063

    Abstract: Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in ... ...

    Abstract Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in several cancers, emerging as a promising pancancer biomarker. However, the requirements for any biomarker are clear methodology, proven feasibility, and reliability. In 357 patients' samples, we studied tertiary lymphoid structures (TLSs) parameters using multiplex immunofluorescence (mIF), hematoxylin-eosin-saffron (HES) staining, double CD20/CD23 staining, and single CD23 immunohistochemistry. The cohort included carcinomas (n = 211) and sarcomas (n = 146), gathering biopsies (n = 170), and surgical specimens (n = 187). mTLSs were defined as TLSs containing either a visible germinal center on HES staining or CD23+ follicular dendritic cells. Focusing on 40 TLSs assessed using mIF, double CD20/CD23 staining was less sensitive than mIF to assess maturity in 27.5% (n = 11/40) but was rescued by single CD23 staining in 90.9% (n = 10/11). In 97 patients, several samples (n = 240) were reviewed to characterize TLS distribution. The likelihood of finding TLSs in surgical material was 6.1 higher than in biopsy and 2.0 higher in primary samples than in metastasis after adjustment with a type of sample. Interrater agreement rates over 4 examiners were 0.65 (Fleiss kappa, 95% CI [0.46, 0.90]) for the presence of TLS and 0.90 for maturity (95% CI [0.83, 0.99]). In this study, we propose a standardized method to screen mTLSs in cancer samples using HES staining and immunohistochemistry that can be applied to all specimens.
    MeSH term(s) Humans ; Tertiary Lymphoid Structures/pathology ; Prognosis ; Reproducibility of Results ; Early Detection of Cancer ; Neoplasms/pathology ; Biomarkers ; Tumor Microenvironment
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-01-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1016/j.labinv.2023.100063
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  7. Article ; Online: Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression.

    Vanhersecke, Lucile / Brunet, Maxime / Guégan, Jean-Philippe / Rey, Christophe / Bougouin, Antoine / Cousin, Sophie / Moulec, Sylvestre Le / Besse, Benjamin / Loriot, Yohann / Larroquette, Mathieu / Soubeyran, Isabelle / Toulmonde, Maud / Roubaud, Guilhem / Pernot, Simon / Cabart, Mathilde / Chomy, François / Lefevre, Corentin / Bourcier, Kevin / Kind, Michèle /
    Giglioli, Ilenia / Sautès-Fridman, Catherine / Velasco, Valérie / Courgeon, Félicie / Oflazoglu, Ezoglin / Savina, Ariel / Marabelle, Aurélien / Soria, Jean-Charles / Bellera, Carine / Sofeu, Casimir / Bessede, Alban / Fridman, Wolf H / Loarer, François Le / Italiano, Antoine

    Nature cancer

    2021  Volume 2, Issue 8, Page(s) 794–802

    Abstract: Only a minority of patients derive long-term clinical benefit from anti-PD1/PD-L1 monoclonal antibodies. The presence of tertiary lymphoid structures (TLS) has been associated with improved survival in several tumor types. Here, using a large-scale ... ...

    Abstract Only a minority of patients derive long-term clinical benefit from anti-PD1/PD-L1 monoclonal antibodies. The presence of tertiary lymphoid structures (TLS) has been associated with improved survival in several tumor types. Here, using a large-scale retrospective analysis of three independent cohorts of cancer patients treated with anti-PD1/PD-L1 antibodies, we showed that the presence of mature TLS was associated with improved objective response rate, progression-free survival, and overall survival independently of PD-L1 expression status and CD8+ T-cell density. These results pave the way for using TLS detection to select patients who are more likely to benefit from immune checkpoint blockade.
    MeSH term(s) Antibodies, Monoclonal/therapeutic use ; B7-H1 Antigen/therapeutic use ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Lung Neoplasms/drug therapy ; Retrospective Studies ; Tertiary Lymphoid Structures
    Chemical Substances Antibodies, Monoclonal ; B7-H1 Antigen ; Immune Checkpoint Inhibitors
    Language English
    Publishing date 2021-08-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2662-1347
    ISSN (online) 2662-1347
    DOI 10.1038/s43018-021-00232-6
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