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  1. Article: With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment.

    Harper, Elizabeth I / Sheedy, Emma F / Stack, M Sharon

    Cancers

    2018  Volume 10, Issue 7

    Abstract: Age is one of the biggest risk factors for ovarian cancer. Older women have higher rates of diagnosis and death associated with the disease. In mouse models, it was shown that aged mice had greater tumor burden than their younger counterparts when ... ...

    Abstract Age is one of the biggest risk factors for ovarian cancer. Older women have higher rates of diagnosis and death associated with the disease. In mouse models, it was shown that aged mice had greater tumor burden than their younger counterparts when intraperitoneally injected with ovarian tumor cells. While very few papers have been published looking at the direct link between ovarian cancer metastasis and age, there is a wealth of information on how age affects metastatic microenvironments. Mesothelial cells, the peritoneal extracellular matrix (ECM), fibroblasts, adipocytes and immune cells all exhibit distinct changes with age. The aged peritoneum hosts a higher number of senescent cells than its younger counterpart, in both the mesothelium and the stroma. These senescent cells promote an inflammatory profile and overexpress Matrix Metalloproteinases (MMPs), which remodel the ECM. The aged ECM is also modified by dysregulated collagen and laminin synthesis, increases in age-related crosslinking and increasing ovarian cancer invasion into the matrix. These changes contribute to a vastly different microenvironment in young and aged models for circulating ovarian cancer cells, creating a more welcoming “soil”.
    Language English
    Publishing date 2018-07-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers10070230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq.

    Luo, Xiaoyu / Frouard, Julie / Zhang, Gang / Neidleman, Jason / Xie, Guorui / Sheedy, Emma / Roan, Nadia R / Greene, Warner C

    Frontiers in immunology

    2022  Volume 13, Page(s) 883420

    Abstract: CD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell ... ...

    Abstract CD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell subsets using mass cytometry and single-cell RNA-seq. CD4 T cell subsets preferentially killed by HIV are phenotypically distinct from those resistant to HIV-associated cell death, in a manner not fully accounted for by their susceptibility to productive infection. Preferentially-killed subsets express CXCR5 and CXCR4 while preferentially-infected subsets exhibit an activated and exhausted effector memory cell phenotype. Single-cell RNA-seq analysis reveals that the subsets of preferentially-killed cells express genes favoring abortive infection and pyroptosis. These studies emphasize a complex interplay between HIV and distinct tissue-based CD4 T cell subsets, and the important contribution of abortive infection and inflammatory programmed cell death to the overall depletion of CD4 T cells that accompanies untreated HIV infection.
    MeSH term(s) CD4-Positive T-Lymphocytes ; HIV Infections ; HIV-1/physiology ; Humans ; RNA-Seq ; T-Lymphocyte Subsets
    Language English
    Publishing date 2022-06-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.883420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Another Wrinkle with Age: Aged Collagen and Intra-peritoneal Metastasis of Ovarian Cancer.

    Harper, Elizabeth I / Hilliard, Tyvette S / Sheedy, Emma F / Carey, Preston / Wilkinson, Paul / Siroky, Michael D / Yang, Jing / Agadi, Elizabeth / Leonard, Annemarie K / Low, Ethan / Liu, Yueying / Biragyn, Arya / Annunziata, Christina M / Stack, M Sharon

    Aging and cancer

    2022  Volume 3, Issue 2, Page(s) 116–129

    Abstract: Background: Age is the most significant risk factor for ovarian cancer (OvCa), the deadliest gynecologic malignancy. Metastasizing OvCa cells adhere to the omentum, a peritoneal structure rich in collagen, adipocytes, and immune cells. Ultrastructural ... ...

    Abstract Background: Age is the most significant risk factor for ovarian cancer (OvCa), the deadliest gynecologic malignancy. Metastasizing OvCa cells adhere to the omentum, a peritoneal structure rich in collagen, adipocytes, and immune cells. Ultrastructural changes in the omentum and the omental collagen matrix with aging have not been evaluated.
    Aim: The aim of this study was to test the hypothesis that age-related changes in collagen in the ovarian tumor microenvironment promote OvCa metastatic success in the aged host.
    Methods/results: Young (3-6 months) and aged mice (20-23 months) were used to study the role of aging in metastatic success. Intra-peritoneal (IP) injection of ID8
    Conclusions: Our results demonstrate that tumors in an aged host can grow with minimal collagen remodeling, while tumors in the young host must remodel peri-tumoral collagen to enable effective proliferation, providing a mechanism whereby age-induced ultrastructural changes in collagen and collagen-rich omenta establish a permissive pre-metastatic niche contributing to enhanced OvCa metastatic success in the aged host.
    Language English
    Publishing date 2022-04-19
    Publishing country United States
    Document type Journal Article
    ISSN 2643-8909
    ISSN (online) 2643-8909
    DOI 10.1002/aac2.12049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Aging Increases Susceptibility to Ovarian Cancer Metastasis in Murine Allograft Models and Alters Immune Composition of Peritoneal Adipose Tissue.

    Loughran, Elizabeth A / Leonard, Annemarie K / Hilliard, Tyvette S / Phan, Ryan C / Yemc, Madeleine G / Harper, Elizabeth / Sheedy, Emma / Klymenko, Yuliya / Asem, Marwa / Liu, Yueying / Yang, Jing / Johnson, Jeff / Tarwater, Laura / Shi, Zonggao / Leevy, Matthew / Ravosa, Matthew J / Stack, M Sharon

    Neoplasia (New York, N.Y.)

    2018  Volume 20, Issue 6, Page(s) 621–631

    Abstract: Ovarian cancer, the most deadly gynecological malignancy in U.S. women, metastasizes uniquely, spreading through the peritoneal cavity and often generating widespread metastatic sites before diagnosis. The vast majority of ovarian cancer cases occur in ... ...

    Abstract Ovarian cancer, the most deadly gynecological malignancy in U.S. women, metastasizes uniquely, spreading through the peritoneal cavity and often generating widespread metastatic sites before diagnosis. The vast majority of ovarian cancer cases occur in women over 40 and the median age at diagnosis is 63. Additionally, elderly women receive poorer prognoses when diagnosed with ovarian cancer. Despite age being a significant risk factor for the development of this cancer, there are little published data which address the impact of aging on ovarian cancer metastasis. Here we report that the aged host is more susceptible to metastatic success using two murine syngeneic allograft models of ovarian cancer metastasis. This age-related increase in metastatic tumor burden corresponds with an increase in tumor infiltrating lymphocytes (TILs) in tumor-bearing mice and alteration of B cell-related pathways in gonadal adipose tissue. Based on this work, further studies elucidating the status of B cell TILs in mouse models of metastasis and human tumors in the context of aging are warranted.
    MeSH term(s) Adipose Tissue/pathology ; Adult ; Aged ; Aging/pathology ; Allografts/pathology ; Animals ; Cell Line ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/pathology ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Neoplasm Metastasis/pathology ; Ovarian Neoplasms/pathology ; Prognosis ; Risk Factors ; Tumor Burden/physiology ; Young Adult
    Language English
    Publishing date 2018-05-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2018.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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