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  1. Article ; Online: Ovarian Cancer: From Precursor Lesion Identification to Population-Based Prevention Programs.

    Sowamber, Ramlogan / Lukey, Alexandra / Huntsman, David / Hanley, Gillian

    Current oncology (Toronto, Ont.)

    2023  Volume 30, Issue 12, Page(s) 10179–10194

    Abstract: Epithelial ovarian cancer (EOC) is a heterogeneous group of malignancies, including high-grade serous ovarian cancer (HGSC). HGSC is often diagnosed at advanced stages and is linked to TP53 variants. ... ...

    Abstract Epithelial ovarian cancer (EOC) is a heterogeneous group of malignancies, including high-grade serous ovarian cancer (HGSC). HGSC is often diagnosed at advanced stages and is linked to TP53 variants. While
    MeSH term(s) Humans ; Female ; Fallopian Tube Neoplasms/pathology ; Cohort Studies ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/prevention & control ; Ovarian Neoplasms/pathology ; Fallopian Tubes/pathology ; Salpingectomy
    Language English
    Publishing date 2023-11-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1236972-x
    ISSN 1718-7729 ; 1198-0052
    ISSN (online) 1718-7729
    ISSN 1198-0052
    DOI 10.3390/curroncol30120741
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: CCAAT/enhancer binding protein delta (C/EBPδ) demonstrates a dichotomous role in tumour initiation and promotion of epithelial carcinoma.

    Sowamber, Ramlogan / Chehade, Rania / Bitar, Mahmoud / Dodds, Leah V / Milea, Anca / Slomovitz, Brian / Shaw, Patricia A / George, Sophia H L

    EBioMedicine

    2019  Volume 44, Page(s) 261–274

    Abstract: Background: CCAAT/enhancer binding protein delta (C/EBPδ,CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinomas of the ovary (HGSC). ... ...

    Abstract Background: CCAAT/enhancer binding protein delta (C/EBPδ,CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinomas of the ovary (HGSC). Overexpression of C/EBPδ in different tumours, such as glioblastoma and breast cancer either promotes tumour progression or inhibits growth and has low expression in normal tissue until activated by cytotoxic stressors.
    Methods: Higher overall expression of C/EBPδ in the luteal phase of the menstrual cycle prompted us to investigate the role of C/EBPδ in carcinogenesis. In vitro experiments were conducted in fallopian tube cell samples and cancer cell lines to investigate the role of C/EBPδ in proliferation, migration, and the epithelial to mesenchymal transition.
    Findings: Expression of C/EBPδ induced premature cellular arrest and decreased soft agar colony formation. Loss of C/EBPδ in epithelial cancer cell lines did not have significant effects on proliferation, yet overexpression demonstrated downregulation of growth, similar to normal fallopian tube cells. C/EBPδ promoted a partial mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating Vimentin and N-cadherin in FTE cells and increased migratory activity, which suggests a regulatory role in the epithelial-mesenchymal plasticity of these cells.
    Interpretation: Our findings suggest that C/EBPδ regulates the phenotype of normal fallopian tube cells by acting on downstream regulatory factors that are implicated in the development of ovarian serous carcinogenesis. FUND: This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), the Princess Margaret Cancer Centre Foundation, Foundation for Women's Cancer - The Belinda-Sue/Mary-Jane Walker Fund, Colleen's Dream Foundation and Sylvester Comprehensive Cancer Center.
    MeSH term(s) Biomarkers, Tumor ; CCAAT-Enhancer-Binding Protein-delta/metabolism ; Carcinoma/etiology ; Carcinoma/metabolism ; Carcinoma/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Models, Biological ; Mucous Membrane/metabolism ; Mucous Membrane/pathology ; Neoplasm Grading ; Phenotype ; RNA Interference
    Chemical Substances Biomarkers, Tumor ; CCAAT-Enhancer-Binding Protein-delta (142662-43-9)
    Language English
    Publishing date 2019-05-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2019.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The vaginal microbiome is associated with endometrial cancer grade and histology.

    Hakimjavadi, Hesamedin / George, Sophia H / Taub, Michael / Dodds, Leah V / Sanchez-Covarrubias, Alex P / Huang, Marilyn / Pearson, J Matt / Slomovitz, Brian M / Kobetz, Erin N / Gharaibeh, Raad / Sowamber, Ramlogan / Pinto, Andre / Chamala, Srikar / Schlumbrecht, Matthew P

    Cancer research communications

    2022  Volume 2, Issue 6, Page(s) 447–455

    Abstract: The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time ...

    Abstract The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.
    MeSH term(s) Humans ; Female ; Endometrial Neoplasms/genetics ; Vagina/microbiology ; Hysterectomy ; Microbiota/genetics ; Carcinoma
    Language English
    Publishing date 2022-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2767-9764
    ISSN (online) 2767-9764
    DOI 10.1158/2767-9764.CRC-22-0075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla-Site of Origin of Serous Carcinoma of the Ovary.

    Sowamber, Ramlogan / Nelson, Omar / Dodds, Leah / DeCastro, Victoria / Paudel, Iru / Milea, Anca / Considine, Michael / Cope, Leslie / Pinto, Andre / Schlumbrecht, Matthew / Slomovitz, Brian / Shaw, Patricia A / George, Sophia H L

    Cancers

    2020  Volume 12, Issue 5

    Abstract: Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the ... ...

    Abstract Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.
    Language English
    Publishing date 2020-04-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12051090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A distinct innate lymphoid cell population regulates tumor-associated T cells.

    Crome, Sarah Q / Nguyen, Linh T / Lopez-Verges, Sandra / Yang, S Y Cindy / Martin, Bernard / Yam, Jennifer Y / Johnson, Dylan J / Nie, Jessica / Pniak, Michael / Yen, Pei Hua / Milea, Anca / Sowamber, Ramlogan / Katz, Sarah Rachel / Bernardini, Marcus Q / Clarke, Blaise A / Shaw, Patricia A / Lang, Philipp A / Berman, Hal K / Pugh, Trevor J /
    Lanier, Lewis L / Ohashi, Pamela S

    Nature medicine

    2017  Volume 23, Issue 3, Page(s) 368–375

    Abstract: Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a ...

    Abstract Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56
    MeSH term(s) CD3 Complex/metabolism ; CD56 Antigen/metabolism ; Cell Proliferation ; Cytokines/immunology ; Flow Cytometry ; Humans ; Immune Tolerance ; Immunity, Innate/immunology ; Immunotherapy ; Interleukins/immunology ; Killer Cells, Natural/immunology ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Natural Cytotoxicity Triggering Receptor 1/metabolism ; Neoplasms/immunology ; Neoplasms/therapy ; T-Lymphocytes/immunology ; Tumor Microenvironment/immunology ; Interleukin-22
    Chemical Substances CD3 Complex ; CD56 Antigen ; Cytokines ; Interleukins ; NCR1 protein, human ; Natural Cytotoxicity Triggering Receptor 1
    Language English
    Publishing date 2017-02-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm.4278
    Database MEDical Literature Analysis and Retrieval System OnLINE

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