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  1. Article ; Online: Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

    Cai, Liuyang / Zhu, Hengyan / Mou, Qianqian / Wong, Po Yee / Lan, Linlin / Ng, Cherrie W K / Lei, Pu / Cheung, Man Kit / Wang, Daijuanru / Wong, Eddy W Y / Lau, Eric H L / Yeung, Zenon W C / Lai, Ronald / Meehan, Katie / Fung, Sherwood / Chan, Kwan Chee A / Lui, Vivian W Y / Cheng, Alfred S L / Yu, Jun /
    Chan, Paul K S / Chan, Jason Y K / Chen, Zigui

    NPJ biofilms and microbiomes

    2024  Volume 10, Issue 1, Page(s) 39

    Abstract: Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic ... ...

    Abstract Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.
    MeSH term(s) Humans ; Squamous Cell Carcinoma of Head and Neck/genetics ; Epigenomics ; Dysbiosis ; Mouth Neoplasms/genetics ; Mouth Neoplasms/metabolism ; Mouth Neoplasms/pathology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Bacteria ; Fusobacterium nucleatum ; Head and Neck Neoplasms/genetics ; Epigenesis, Genetic ; Microbiota ; Tumor Microenvironment
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2817021-0
    ISSN 2055-5008 ; 2055-5008
    ISSN (online) 2055-5008
    ISSN 2055-5008
    DOI 10.1038/s41522-024-00511-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Clinical utility of circulating Epstein-Barr virus DNA analysis for the management of nasopharyngeal carcinoma.

    Fung, Sherwood Y H / Lam, Jacky W K / Chan, Kwan Chee Allen

    Chinese clinical oncology

    2016  Volume 5, Issue 2, Page(s) 18

    Abstract: Nasopharyngeal carcinoma (NPC) is one of the commonest cancers in Southern China. The carcinogenesis is closely associated with Epstein-Barr virus (EBV) infection. In endemic regions with high incidence of NPC, EBV genome can be detected in virtually all ...

    Abstract Nasopharyngeal carcinoma (NPC) is one of the commonest cancers in Southern China. The carcinogenesis is closely associated with Epstein-Barr virus (EBV) infection. In endemic regions with high incidence of NPC, EBV genome can be detected in virtually all NPC tumor tissues. Over the last decade, circulating cell-free EBV DNA has been developed as a tumor marker for NPC. Plasma EBV DNA analysis using real-time PCR has been shown to be useful for early detection, prognostication and monitoring of treatment response of NPC. In this review, the clinical applications of EBV DNA analysis in the management of NPC would be discussed.
    MeSH term(s) Carcinoma ; DNA, Viral/blood ; Early Detection of Cancer/methods ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/genetics ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/pathogenicity ; Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/pathology ; Nasopharyngeal Neoplasms/virology ; Prognosis
    Chemical Substances DNA, Viral
    Language English
    Publishing date 2016-04-27
    Publishing country China
    Document type Journal Article ; Review
    ZDB-ID 2828547-5
    ISSN 2304-3873 ; 2304-3865
    ISSN (online) 2304-3873
    ISSN 2304-3865
    DOI 10.21037/cco.2016.03.07
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Testing for EGFR Variants in Pleural and Pericardial Effusion Cell-Free DNA in Patients With Non-Small Cell Lung Cancer.

    Lee, Kirsty W C / Li, Molly S C / Gai, Wanxia / Lau, Yat Ming / Chan, Allen K C / Chan, Oscar S H / Lee, Chee Khoon / Yeung, Rebecca M W / Fung, Sherwood Y H / Cheung, Wai F / Chan, Vivian W / Leung, Linda / Kam, Kenny N P / Mok, Tony S K

    JAMA oncology

    2022  Volume 9, Issue 2, Page(s) 261–265

    Abstract: Importance: Molecular testing in non-small cell lung cancer (NSCLC) is commonly limited by inadequate tumor sample. Plasma cell-free DNA (cfDNA) genotyping as a complementary test is specific but only moderately sensitive. Genotyping of cfDNA in pleural ...

    Abstract Importance: Molecular testing in non-small cell lung cancer (NSCLC) is commonly limited by inadequate tumor sample. Plasma cell-free DNA (cfDNA) genotyping as a complementary test is specific but only moderately sensitive. Genotyping of cfDNA in pleural and pericardial effusion (PE-cfDNA) can further optimize molecular diagnostic yield and reduce the need for repeated biopsies.
    Objective: To prospectively validate droplet digital polymerase chain reaction (ddPCR) for detection of sensitizing EGFR variants and acquired Thr790Met variant (T790M) from PE-cfDNA in patients with NSCLC.
    Design, setting, and participants: This prospective diagnostic validation study was conducted between September 6, 2016, and January 21, 2021 at 2 major Hong Kong cancer centers. Patients with advanced NSCLC with both wild-type and variant EGFR status and exudative PE who underwent thoracocentesis or pericardiocentesis were randomly enrolled. Patients were either EGFR-tyrosine kinase inhibitor (TKI) naive (cohort 1) or EGFR-TKI treated but osimertinib naive (cohort 2). Enrolled patients underwent pleural- or pericardial-fluid and blood sampling for ddPCR EGFR testing. EGFR status results with ddPCR testing of PE-cfDNA and blood were compared with EGFR status in matched tumor biopsy or PE cell block samples.
    Main outcomes and measures: Specificity, sensitivity, and concordance of PE-cfDNA for detection of sensitizing EGFR variants and acquired T790M variation.
    Results: Among 171 patients (54% female) enrolled, there were 104 in cohort 1 and 67 in cohort 2. In cohort 1, 37% (38/102) were EGFR-variant positive; PE-cfDNA showed 97% sensitivity (95% CI, 92%-100%), 97% specificity (95% CI, 93%-100%), and 97% concordance (ĸ = 0.94, P < .001) for the detection of sensitizing EGFR variants. It was more sensitive than plasma in detecting sensitizing EGFR variants (97% vs 74%, P < .001). In cohort 2, 38% (15 of 40) were positive for the EGFR T790M variant; PE-cfDNA showed 87% sensitivity (95% CI, 69%-100%), 60% specificity (95% CI, 41%-79%), and 70% concordance (ĸ = 0.42, P = .004) for acquired T790M. The EGFR T790M variant was detected in 51% of PE-cfDNA vs 25% of PE cell block samples.
    Conclusions and relevance: In this diagnostic study, EGFR variants could be accurately detected from PE-cfDNA in patients with NSCLC. More EGFR T790M was detected in PE-cfDNA than in guideline-recommended PE cell block preparations. These results suggest that PE-cfDNA can complement plasma and tumor genotyping for detecting EGFR variants in patients with advanced NSCLC.
    MeSH term(s) Humans ; Female ; Male ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Cell-Free Nucleic Acids/genetics ; Pericardial Effusion/genetics ; ErbB Receptors/genetics ; Prospective Studies ; Protein Kinase Inhibitors/therapeutic use ; Drug Resistance, Neoplasm/genetics ; Mutation
    Chemical Substances Cell-Free Nucleic Acids ; ErbB Receptors (EC 2.7.10.1) ; Protein Kinase Inhibitors ; EGFR protein, human (EC 2.7.10.1)
    Language English
    Publishing date 2022-12-29
    Publishing country United States
    Document type Journal Article
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2022.6109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Droplet digital PCR of tumor suppressor gene methylation in serial oral rinses of patients with head and neck squamous cell carcinoma.

    Fung, Sherwood Y H / Chan, Kwan Chee Allen / Wong, Eddy W Y / Ng, Cherrie W K / Cho, Ryan / Yeung, Zenon W C / Lam, Jacky W K / Chan, Jason Y K

    Head & neck

    2021  Volume 43, Issue 6, Page(s) 1812–1822

    Abstract: Background: Head and neck squamous cell carcinoma (HNSCC) currently lacks sensitive approaches to detect cancer-related traits in body fluid.: Methods: Methylation of tumor suppressor genes (TSGs) (PAX5, EDNRB, and DCC) were measured in the oral ... ...

    Abstract Background: Head and neck squamous cell carcinoma (HNSCC) currently lacks sensitive approaches to detect cancer-related traits in body fluid.
    Methods: Methylation of tumor suppressor genes (TSGs) (PAX5, EDNRB, and DCC) were measured in the oral rinses from 50 HNSCC and 58 control subjects using droplet digital PCR (ddPCR). Diagnostic accuracies in detecting HNSCC and the detection rate of recurrence in the post-treatment monitoring were analyzed.
    Results: ddPCR TSG methylation detection in oral rinses for diagnosis of HNSCC had an AUC of 0.892 for PAX5, 0.753 for EDNRB, and 0.729 for DCC. Significant drop of TSG methylation was observed after completion of surgery (p < 0.01). 76.9% of the relapse cases had a pre-emptive rebound of methylation above presurgery levels in at least one of the tested markers before confirmed recurrence.
    Conclusions: Utilizing ddPCR for TSG methylation detection in oral rinses shows potential for detection and monitoring of HNSCC.
    MeSH term(s) Carcinoma, Squamous Cell/genetics ; DNA Methylation ; Genes, Tumor Suppressor ; Head and Neck Neoplasms/genetics ; Humans ; Neoplasm Recurrence, Local/genetics ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Squamous Cell Carcinoma of Head and Neck/genetics
    Language English
    Publishing date 2021-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645165-2
    ISSN 1097-0347 ; 0148-6403 ; 1043-3074
    ISSN (online) 1097-0347
    ISSN 0148-6403 ; 1043-3074
    DOI 10.1002/hed.26647
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Restoration of the Oral Microbiota After Surgery for Head and Neck Squamous Cell Carcinoma Is Associated With Patient Outcomes.

    Chan, Jason Y K / Ng, Cherrie W K / Lan, Linlin / Fung, Sherwood / Li, Jing-Woei / Cai, Liuyang / Lei, Pu / Mou, Qianqian / Meehan, Katie / Lau, Eric H L / Yeung, Zenon / Chan, K C Allen / Wong, Eddy W Y / Chan, Paul K S / Chen, Zigui

    Frontiers in oncology

    2021  Volume 11, Page(s) 737843

    Abstract: Objective: To evaluate the dynamics of the oral microbiome and associated patient outcomes following treatment of head and neck squamous cell carcinoma (HNSCC).: Materials and methods: This was a prospective cohort study at a tertiary academic center ...

    Abstract Objective: To evaluate the dynamics of the oral microbiome and associated patient outcomes following treatment of head and neck squamous cell carcinoma (HNSCC).
    Materials and methods: This was a prospective cohort study at a tertiary academic center in Hong Kong SAR of patients with head and neck squamous cell carcinoma evaluating the oral microbiome in pre- and postsurgery oral rinses (at 1, 3, and 6 months) with 16S rRNA gene V3-V4 amplicon sequencing.
    Results: In total, 76 HNSCC patients were evaluated. There was a significantly depressed alpha diversities of oral microbial communities observed in HNSCC oral rinse samples within the first 6 months post-surgery when compared to presurgery or healthy controls. Distant clustering between pre- and postsurgery was also observed (
    Conclusions: Oral microbiome dysbiosis associated with HNSCC is dynamic. These dynamics of the oral microbiome postsurgery are also associated with patient treatment and outcomes and may serve as potential biomarkers for patient management in HNSCC.
    Language English
    Publishing date 2021-10-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.737843
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma.

    Chen, Zigui / Wong, Po Yee / Ng, Cherrie W K / Lan, Linlin / Fung, Sherwood / Li, Jing W / Cai, Liuyang / Lei, Pu / Mou, Qianqian / Wong, Sunny H / Wu, William K K / Li, Ryan J / Meehan, Katie / Lui, Vivian W Y / Chow, Chit / Lo, Kwok W / Chan, Amy B W / Boon, Siaw Shi / Lau, Eric H L /
    Yeung, Zenon / Chan, Kwan C Allen / Wong, Eddy W Y / Cheng, Alfred S L / Yu, Jun / Chan, Paul K S / Chan, Jason Y K

    Cancers

    2020  Volume 12, Issue 11

    Abstract: The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a ... ...

    Abstract The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of
    Language English
    Publishing date 2020-11-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12113425
    Database MEDical Literature Analysis and Retrieval System OnLINE

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