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  1. AU="Aitor Rodriguez-Casanova"
  2. AU="Wimpenny, Claire"
  3. AU=Gao W J
  4. AU="Suarez-Almazor, Maria E"
  5. AU="Barciszewski, Jakub"
  6. AU=Madhusoodanan Jyoti
  7. AU="Korbecki, Jan"

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  1. Artikel ; Online: Publisher Correction

    Aida Bao-Caamano / Nicolás Costa-Fraga / Laure Cayrefourcq / María Amalia Jácome / Aitor Rodriguez-Casanova / Laura Muinelo-Romay / Rafael López-López / Catherine Alix-Panabières / Angel Díaz-Lagares

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer

    2023  Band 6

    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2023-10-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Epigenomic reprogramming of therapy-resistant circulating tumor cells in colon cancer

    Aida Bao-Caamano / Nicolás Costa-Fraga / Laure Cayrefourcq / Aitor Rodriguez-Casanova / Laura Muinelo-Romay / Rafael López-López / Catherine Alix-Panabières / Angel Díaz-Lagares

    Frontiers in Cell and Developmental Biology, Vol

    2023  Band 11

    Abstract: Therapy resistance is a major challenge in colorectal cancer management. Epigenetic changes, such as DNA methylation, in tumor cells are involved in the development of acquired resistance during treatment. Here, we characterized the DNA methylation ... ...

    Abstract Therapy resistance is a major challenge in colorectal cancer management. Epigenetic changes, such as DNA methylation, in tumor cells are involved in the development of acquired resistance during treatment. Here, we characterized the DNA methylation landscape of colon circulating tumor cells (CTCs) during cancer progression and therapy resistance development. To this aim, we used nine permanent CTC lines that were derived from peripheral blood samples of a patient with metastatic colon cancer collected before treatment initiation (CTC-MCC-41) and during treatment and cancer progression (CTC-MCC-41.4 and CTC-MCC-41.5 [A-G]). We analyzed the DNA methylome of these nine CTC lines using EPIC arrays and also assessed the association between DNA methylation and gene expression profiles. We confirmed DNA methylation and gene expression results by pyrosequencing and RT-qPCR, respectively. The global DNA methylation profiles were different in the pre-treatment CTC line and in CTC lines derived during therapy resistance development. These resistant CTC lines were characterized by a more hypomethylated profile compared with the pre-treatment CTC line. Most of the observed DNA methylation differences were localized at CpG-poor regions and some in CpG islands, shore regions and promoters. We identified a distinctive DNA methylation signature that clearly differentiated the pre-treatment CTC line from the others. Of note, the genes involved in this signature were associated with cancer-relevant pathways, including PI3K/AKT, MAPK, Wnt signaling and metabolism. We identified several epigenetically deregulated genes associated with therapy resistance in CTCs, such as AP2M1. Our results bring new knowledge on the epigenomic landscape of therapy-resistant CTCs, providing novel mechanisms of resistance as well as potential biomarkers and therapeutic targets for advanced CRC management.
    Schlagwörter Epigenomics ; DNA methylation ; metastasis-competent CTCs ; colorectal cancer ; biomarkers ; therapeutic targets ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-12-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer

    Aida Bao-Caamano / Nicolás Costa-Fraga / Laure Cayrefourcq / María Amalia Jácome / Aitor Rodriguez-Casanova / Laura Muinelo-Romay / Rafael López-López / Catherine Alix-Panabières / Angel Díaz-Lagares

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Band 13

    Abstract: Abstract Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis- ... ...

    Abstract Abstract Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis-competent CTCs in CRC. The DNA methylome of the human CRC-derived cell line CTC-MCC-41 was analyzed and compared with primary (HT29, Caco2, HCT116, RKO) and metastatic (SW620 and COLO205) CRC cells. The association between methylation and the transcriptional profile of CTC-MCC-41 was also evaluated. Differentially methylated CpGs were validated with pyrosequencing and qMSP. Compared to primary and metastatic CRC cells, the methylation profile of CTC-MCC-41 was globally different and characterized by a slight predominance of hypomethylated CpGs mainly distributed in CpG-poor regions. Promoter CpG islands and shore regions of CTC-MCC-41 displayed a unique methylation profile that was associated with the transcriptional program and relevant cancer pathways, mainly Wnt signaling. The epigenetic regulation of relevant genes in CTC-MCC-41 was validated. This study provides new insights into the epigenomic landscape of metastasis-competent CTCs, revealing biological information for metastasis development, as well as new potential biomarkers and therapeutic targets for CRC patients.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2023-09-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer

    Aitor Rodriguez-Casanova / Nicolás Costa-Fraga / Aida Bao-Caamano / Rafael López-López / Laura Muinelo-Romay / Angel Diaz-Lagares

    Frontiers in Cell and Developmental Biology, Vol

    2021  Band 9

    Abstract: Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of ...

    Abstract Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.
    Schlagwörter epigenetics ; liquid biopsy ; biomarkers ; colorectal cancer ; precision oncology ; circulating nucleic acids ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-02-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Evaluation of a Targeted Next-Generation Sequencing Panel for the Non-Invasive Detection of Variants in Circulating DNA of Colorectal Cancer

    Aitor Rodríguez-Casanova / Aida Bao-Caamano / Ramón M. Lago-Lestón / Elena Brozos-Vázquez / Nicolás Costa-Fraga / Isabel Ferreirós-Vidal / Ihab Abdulkader / Yolanda Vidal-Insua / Francisca Vázquez Rivera / Sonia Candamio Folgar / Rafael López-López / Laura Muinelo-Romay / Angel Diaz-Lagares

    Journal of Clinical Medicine, Vol 10, Iss 4487, p

    2021  Band 4487

    Abstract: Molecular profiling of circulating cell-free DNA (cfDNA) has shown utility for the management of colorectal cancer (CRC). TruSight Tumor 170 (TST170) is a next-generation sequencing (NGS) panel that covers 170 cancer-related genes, including KRAS , which ...

    Abstract Molecular profiling of circulating cell-free DNA (cfDNA) has shown utility for the management of colorectal cancer (CRC). TruSight Tumor 170 (TST170) is a next-generation sequencing (NGS) panel that covers 170 cancer-related genes, including KRAS , which is a key driver gene in CRC. We evaluated the capacity of TST170 to detect gene variants in cfDNA from a retrospective cohort of 20 metastatic CRC patients with known KRAS variants in tumor tissue and in cfDNA previously analyzed by pyrosequencing and BEAMing, respectively. The cfDNA of most of the patients (95%) was successfully sequenced. We frequently detected variants with clinical significance in KRAS (79%, 15/19) and PIK3CA (26%, 5/19) genes. Variants with potential clinical significance were also identified in another 27 cancer genes, such as APC . The type of KRAS variant detected in cfDNA by TST170 showed high concordance with those detected in tumor tissue (77%), and very high concordance with cfDNA analyzed by BEAMing (94%). The variant allele fractions for KRAS obtained in cfDNA by TST170 and BEAMing correlated strongly. This proof-of-principle study indicates that targeted NGS analysis of cfDNA with TST170 could be useful for non-invasive detection of gene variants in metastatic CRC patients, providing an assay that could be easily implemented for detecting somatic alterations in the clinic.
    Schlagwörter colorectal cancer ; TruSight Tumor 170 ; NGS ; BEAMing ; liquid biopsy ; tumor biomarkers ; Medicine ; R
    Sprache Englisch
    Erscheinungsdatum 2021-09-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture

    Eva G. Álvarez / Jonas Demeulemeester / Paula Otero / Clemency Jolly / Daniel García-Souto / Ana Pequeño-Valtierra / Jorge Zamora / Marta Tojo / Javier Temes / Adrian Baez-Ortega / Bernardo Rodriguez-Martin / Ana Oitaben / Alicia L. Bruzos / Mónica Martínez-Fernández / Kerstin Haase / Sonia Zumalave / Rosanna Abal / Jorge Rodríguez-Castro / Aitor Rodriguez-Casanova /
    Angel Diaz-Lagares / Yilong Li / Keiran M. Raine / Adam P. Butler / Iago Otero / Atsushi Ono / Hiroshi Aikata / Kazuaki Chayama / Masaki Ueno / Shinya Hayami / Hiroki Yamaue / Kazuhiro Maejima / Miguel G. Blanco / Xavier Forns / Carmen Rivas / Juan Ruiz-Bañobre / Sofía Pérez-del-Pulgar / Raúl Torres-Ruiz / Sandra Rodriguez-Perales / Urtzi Garaigorta / Peter J. Campbell / Hidewaki Nakagawa / Peter Van Loo / Jose M. C. Tubio

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Band 12

    Abstract: Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient ... ...

    Abstract Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-11-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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