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  1. Article ; Online: Current challenges and practical aspects of molecular pathology for bone and soft tissue tumors.

    de Álava, Enrique

    Virchows Archiv : an international journal of pathology

    2024  Volume 484, Issue 2, Page(s) 353–367

    Abstract: This review shows the extraordinary change molecular pathology has induced in the classification, diagnosis, and clinical practice of molecular pathologists dealing with sarcomas. We have primarily focused on the practical aspects of molecular studies ... ...

    Abstract This review shows the extraordinary change molecular pathology has induced in the classification, diagnosis, and clinical practice of molecular pathologists dealing with sarcomas. We have primarily focused on the practical aspects of molecular studies and the current and mid-term challenges for our subspecialty, ending with ten tips for the next generation of sarcoma molecular pathologists.
    MeSH term(s) Humans ; Pathology, Molecular ; Sarcoma/diagnosis ; Sarcoma/genetics ; Sarcoma/pathology ; Soft Tissue Neoplasms/diagnosis ; Soft Tissue Neoplasms/genetics ; Soft Tissue Neoplasms/pathology ; Pathologists
    Language English
    Publishing date 2024-01-16
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-024-03736-5
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    In stock of ZB MED Cologne/Königswinter

    Ud III Zs.10: Show issues Location:
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  2. Article ; Online: Identification of Novel/Rare

    Salguero-Aranda, Carmen / Di Blasi, Elena / Galán, Lourdes / Zaldumbide, Laura / Civantos, Gema / Marcilla, David / de Álava, Enrique / Díaz-Martín, Juan

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. ...

    Abstract Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis.
    MeSH term(s) Humans ; Calmodulin-Binding Proteins/genetics ; Chondrosarcoma/genetics ; Neoplasms, Connective and Soft Tissue ; Oncogene Proteins, Fusion/genetics ; RNA-Binding Protein EWS/genetics ; RNA-Binding Proteins/genetics ; Sarcoma/pathology ; Soft Tissue Neoplasms/genetics
    Chemical Substances Calmodulin-Binding Proteins ; EWSR1 protein, human ; Oncogene Proteins, Fusion ; RNA-Binding Protein EWS ; RNA-Binding Proteins
    Language English
    Publishing date 2024-02-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25031735
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  3. Article ; Online: Epithelioid haemangioma after bone surgery: an event not previously described.

    Izquierdo, Francisco Miguel / Casas, Paula / de Álava, Enrique / Romagosa, María Cleofé / Silva, Tulio / Ramos, Luis Rafael

    Pathology

    2024  

    Language English
    Publishing date 2024-03-26
    Publishing country England
    Document type Letter
    ZDB-ID 7085-3
    ISSN 1465-3931 ; 0031-3025
    ISSN (online) 1465-3931
    ISSN 0031-3025
    DOI 10.1016/j.pathol.2024.01.008
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    Zs.A 723: Show issues Location:
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  4. Article ; Online: Ewing Sarcoma, an Update on Molecular Pathology with Therapeutic Implications.

    de Alava, Enrique

    Surgical pathology clinics

    2017  Volume 10, Issue 3, Page(s) 575–585

    Abstract: Ewing sarcoma is a developmental tumor characterized by balanced chromosomal translocations and formation of new fusion genes. Despite the large amount of knowledge regarding the molecular aspects obtained in the last few years, many questions still ... ...

    Abstract Ewing sarcoma is a developmental tumor characterized by balanced chromosomal translocations and formation of new fusion genes. Despite the large amount of knowledge regarding the molecular aspects obtained in the last few years, many questions still remain. This article focuses on research on the molecular pathology and possible developments in targeted therapies in this malignancy and discusses some related bottlenecks, as well as the possible role of pathologists, the availability of samples, the lack of appropriate animal models, and the resources needed to carry out preclinical and clinical research.
    Language English
    Publishing date 2017-09
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1875-9157
    ISSN (online) 1875-9157
    DOI 10.1016/j.path.2017.04.001
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  5. Article: Birth and evolution of the desmoplastic small round-cell tumor.

    de Alava, Enrique / Marcilla, David

    Seminars in diagnostic pathology

    2016  Volume 33, Issue 5, Page(s) 254–261

    Abstract: The first large series of desmoplastic small round cell tumor was reported twenty-five years ago. This article reviews the original characterization of this neoplasm, and the eventual expansion of its clinical and pathological spectrum. Relevant data on ... ...

    Abstract The first large series of desmoplastic small round cell tumor was reported twenty-five years ago. This article reviews the original characterization of this neoplasm, and the eventual expansion of its clinical and pathological spectrum. Relevant data on its molecular features are summarized, in order to understand the search for therapeutic targets. The challenge ahead is to better know and cure this disease through the finding and validation of actionable therapeutic targets.
    MeSH term(s) Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Calmodulin-Binding Proteins/genetics ; Calmodulin-Binding Proteins/metabolism ; Desmin/metabolism ; Desmoplastic Small Round Cell Tumor/genetics ; Desmoplastic Small Round Cell Tumor/metabolism ; Desmoplastic Small Round Cell Tumor/pathology ; Humans ; Keratins/metabolism ; RNA-Binding Protein EWS ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; WT1 Proteins/genetics ; WT1 Proteins/metabolism
    Chemical Substances Biomarkers, Tumor ; Calmodulin-Binding Proteins ; Desmin ; EWSR1 protein, human ; RNA-Binding Protein EWS ; RNA-Binding Proteins ; WT1 Proteins ; Keratins (68238-35-7)
    Language English
    Publishing date 2016-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 605834-6
    ISSN 1930-1111 ; 0740-2570
    ISSN (online) 1930-1111
    ISSN 0740-2570
    DOI 10.1053/j.semdp.2016.05.003
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    Zs.A 1988: Show issues Location:
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  6. Article ; Online: Endoglin in the Spotlight to Treat Cancer.

    González Muñoz, Teresa / Amaral, Ana Teresa / Puerto-Camacho, Pilar / Peinado, Héctor / de Álava, Enrique

    International journal of molecular sciences

    2021  Volume 22, Issue 6

    Abstract: A spotlight has been shone on endoglin in recent years due to that fact of its potential to serve as both a reliable disease biomarker and a therapeutic target. Indeed, endoglin has now been assigned many roles in both physiological and pathological ... ...

    Abstract A spotlight has been shone on endoglin in recent years due to that fact of its potential to serve as both a reliable disease biomarker and a therapeutic target. Indeed, endoglin has now been assigned many roles in both physiological and pathological processes. From a molecular point of view, endoglin mainly acts as a co-receptor in the canonical TGFβ pathway, but also it may be shed and released from the membrane, giving rise to the soluble form, which also plays important roles in cell signaling. In cancer, in particular, endoglin may contribute to either an oncogenic or a non-oncogenic phenotype depending on the cell context. The fact that endoglin is expressed by neoplastic and non-neoplastic cells within the tumor microenvironment suggests new possibilities for targeted therapies. Here, we aimed to review and discuss the many roles played by endoglin in different tumor types, as well as the strong evidence provided by pre-clinical and clinical studies that supports the therapeutic targeting of endoglin as a novel clinical strategy.
    MeSH term(s) Animals ; Biomarkers, Tumor ; Cell Communication ; Endoglin/antagonists & inhibitors ; Endoglin/genetics ; Endoglin/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Liquid Biopsy ; Molecular Targeted Therapy ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism ; Signal Transduction/drug effects ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics
    Chemical Substances Biomarkers, Tumor ; Endoglin
    Language English
    Publishing date 2021-03-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22063186
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  7. Article: Evaluation of

    Salguero-Aranda, Carmen / Martínez-Reguera, Paula / Marcilla, David / de Álava, Enrique / Díaz-Martín, Juan

    Cancers

    2021  Volume 13, Issue 20

    Abstract: Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene ... ...

    Abstract Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion
    Language English
    Publishing date 2021-10-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13205237
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  8. Article ; Online: Small round cell sarcomas.

    Cidre-Aranaz, Florencia / Watson, Sarah / Amatruda, James F / Nakamura, Takuro / Delattre, Olivier / de Alava, Enrique / Dirksen, Uta / Grünewald, Thomas G P

    Nature reviews. Disease primers

    2022  Volume 8, Issue 1, Page(s) 66

    Abstract: Undifferentiated small round cell sarcomas (SRCSs) of bone and soft tissue comprise a heterogeneous group of highly aggressive tumours associated with a poor prognosis, especially in metastatic disease. SRCS entities mainly occur in the third decade of ... ...

    Abstract Undifferentiated small round cell sarcomas (SRCSs) of bone and soft tissue comprise a heterogeneous group of highly aggressive tumours associated with a poor prognosis, especially in metastatic disease. SRCS entities mainly occur in the third decade of life and can exhibit striking disparities regarding preferentially affected sex and tumour localization. SRCSs comprise new entities defined by specific genetic abnormalities, namely EWSR1-non-ETS fusions, CIC-rearrangements or BCOR genetic alterations, as well as EWSR1-ETS fusions in the prototypic SRCS Ewing sarcoma. These gene fusions mainly encode aberrant oncogenic transcription factors that massively rewire the transcriptome and epigenome of the as yet unknown cell or cells of origin. Additional mutations or copy number variants are rare at diagnosis and, depending on the tumour entity, may involve TP53, CDKN2A and others. Histologically, these lesions consist of small round cells expressing variable levels of CD99 and specific marker proteins, including cyclin B3, ETV4, WT1, NKX3-1 and aggrecan, depending on the entity. Besides locoregional treatment that should follow standard protocols for sarcoma management, (neo)adjuvant treatment is as yet ill-defined but generally follows that of Ewing sarcoma and is associated with adverse effects that might compromise quality of life. Emerging studies on the molecular mechanisms of SRCSs and the development of genetically engineered animal models hold promise for improvements in early detection, disease monitoring, treatment-related toxicity, overall survival and quality of life.
    MeSH term(s) Aggrecans ; Humans ; Quality of Life ; Sarcoma/diagnosis ; Sarcoma/genetics ; Sarcoma/therapy ; Sarcoma, Ewing/diagnosis ; Sarcoma, Small Cell/diagnosis ; Sarcoma, Small Cell/genetics ; Sarcoma, Small Cell/pathology ; Transcription Factors
    Chemical Substances Aggrecans ; Transcription Factors
    Language English
    Publishing date 2022-10-06
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ISSN 2056-676X
    ISSN (online) 2056-676X
    DOI 10.1038/s41572-022-00393-3
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  9. Article: Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma.

    Salguero-Aranda, Carmen / Olmedo-Pelayo, Joaquín / de Álava, Enrique / Amaral, Ana Teresa / Díaz-Martín, Juan

    Cancers

    2022  Volume 14, Issue 24

    Abstract: The Hippo pathway is an evolutionarily conserved modulator of developmental biology with a key role in tissue and organ size regulation under homeostatic conditions. Like other signaling pathways with a significant role in embryonic development, the ... ...

    Abstract The Hippo pathway is an evolutionarily conserved modulator of developmental biology with a key role in tissue and organ size regulation under homeostatic conditions. Like other signaling pathways with a significant role in embryonic development, the deregulation of Hippo signaling contributes to oncogenesis. Central to the Hippo pathway is a conserved cascade of adaptor proteins and inhibitory kinases that converge and regulate the activity of the oncoproteins YAP and TAZ, the final transducers of the pathway. Elevated levels and aberrant activation of YAP and TAZ have been described in many cancers. Though most of the studies describe their pervasive activation in epithelial neoplasms, there is increasing evidence pointing out its relevance in mesenchymal malignancies as well. Interestingly, somatic or germline mutations in genes of the Hippo pathway are scarce compared to other signaling pathways that are frequently disrupted in cancer. However, in the case of sarcomas, several examples of genetic alteration of Hippo members, including gene fusions, have been described during the last few years. Here, we review the current knowledge of Hippo pathway implication in sarcoma, describing mechanistic hints recently reported in specific histological entities and how these alterations represent an opportunity for targeted therapy in this heterogeneous group of neoplasm.
    Language English
    Publishing date 2022-12-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14246211
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  10. Article ; Online: Cost-effectiveness analysis of molecular diagnosis by next-generation sequencing versus sequential single testing in metastatic non-small cell lung cancer patients from a south Spanish hospital perspective.

    de Alava, Enrique / Pareja, María Jesús / Carcedo, David / Arrabal, Natalia / García, José-Francisco / Bernabé-Caro, Reyes

    Expert review of pharmacoeconomics & outcomes research

    2022  Volume 22, Issue 6, Page(s) 1033–1042

    Abstract: Background: To assess the cost-effectiveness of using next-generation sequencing (NGS) compared to sequential single-testing (SST) for molecular diagnostic and treatment of patients with advanced non-small cell lung cancer (NSCLC) from a Spanish single- ... ...

    Abstract Background: To assess the cost-effectiveness of using next-generation sequencing (NGS) compared to sequential single-testing (SST) for molecular diagnostic and treatment of patients with advanced non-small cell lung cancer (NSCLC) from a Spanish single-center perspective, the Hospital Universitario Virgen del Rocio (HUVR).
    Research design and methods: A decision-tree model was developed to assess the alterations detection alterations and diagnostic cost in patients with advanced NSCLC, comparing NGS versus SST. Model inputs such as testing, positivity rates, or treatment allocation were obtained from the literature and the clinical practice of HUVR experts through consultation. Several sensitivity analyses were performed to test the robustness of the model.
    Results: Using NGS for molecular diagnosis of a 100-patients hypothetical cohort, 30 more alterations could be detected and 3 more patients could be enrolled in clinical-trials than using SST. On the other hand, diagnostic costs were increased up to €20,072 using NGS instead of SST. Using NGS time-to-results would be reduced from 16.7 to 9 days.
    Conclusions: The implementation of NGS at HUVR for the diagnostic of patients with advanced NSCLC provides significant clinical benefits compared to SST in terms of alterations detected, treatment with targeted-therapies and clinical-trial enrollment, and could be considered a cost-effective strategy.
    MeSH term(s) Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Cost-Benefit Analysis ; High-Throughput Nucleotide Sequencing/methods ; Hospitals ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Mutation
    Language English
    Publishing date 2022-05-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2208481-2
    ISSN 1744-8379 ; 1473-7167
    ISSN (online) 1744-8379
    ISSN 1473-7167
    DOI 10.1080/14737167.2022.2078310
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