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  1. Article ; Online: A Syngeneic Murine Model of Endometriosis using Naturally Cycling Mice.

    Richards, Elliott G / Rehmer, Jenna M / Mathes, Melissa A / Esakov, Emily L / Braley, Chad / Joehlin-Price, Amy / Chiesa-Vottero, Andres / Reizes, Ofer

    Journal of visualized experiments : JoVE

    2020  , Issue 165

    Abstract: Endometriosis is a leading cause of pelvic pain and infertility. It is defined by the presence of endometrial tissue in extrauterine locations. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to ... ...

    Abstract Endometriosis is a leading cause of pelvic pain and infertility. It is defined by the presence of endometrial tissue in extrauterine locations. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to challenges in studying the disease. Outside of primates, few mammals menstruate, and none develop spontaneous endometriosis. Rodent models are popular but require artificial induction of endometriosis, with many utilizing either immunocompromised mice or surgically induced disease. Recently, more attention has been given to models involving intraperitoneal injection. We present a murine model of endometriosis that integrates several features of existing endometriosis models into a novel, simplified system that relies on microscopic quantification in lieu of subjective grading. In this model, we perform hormonal stimulation of donor mice, intraperitoneal injection, systematic abdominal survey and tissue harvest, and histologic quantification that can be performed and verified at any time after necropsy. This model requires minimal resources and training; does not require expertise by lab technicians in murine survival surgery or in the identification of gross endometriotic lesions; can be used in immunocompromised, immunocompetent, and/or mutant mice; and reliably creates endometriotic lesions that are histologically consistent with human endometriotic disease.
    MeSH term(s) Animals ; Disease Models, Animal ; Endometriosis/drug therapy ; Endometriosis/etiology ; Endometriosis/pathology ; Endometrium/pathology ; Female ; Humans ; Image Processing, Computer-Assisted ; Injections, Intraperitoneal ; Mice, Inbred C57BL ; Software
    Language English
    Publishing date 2020-11-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/61960
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A syngeneic murine model of endometriosis using naturally cycling mice

    Richards, Elliott G. / Rehmer, Jenna M. / Mathes, Melissa A. / Esakov, Emily L. / Braley, Chad / Joehlin-Price, Amy / Chiesa-Vottero, Andres / Reizes, Ofer

    Journal of visualized experiments. 2020 Nov. 24, , no. 165

    2020  

    Abstract: Endometriosis is a leading cause of pelvic pain and infertility. It is defined by the presence of endometrial tissue in extrauterine locations. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to ... ...

    Abstract Endometriosis is a leading cause of pelvic pain and infertility. It is defined by the presence of endometrial tissue in extrauterine locations. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to challenges in studying the disease. Outside of primates, few mammals menstruate, and none develop spontaneous endometriosis. Rodent models are popular but require artificial induction of endometriosis, with many utilizing either immunocompromised mice or surgically induced disease. Recently, more attention has been given to models involving intraperitoneal injection. We present a murine model of endometriosis that integrates several features of existing endometriosis models into a novel, simplified system that relies on microscopic quantification in lieu of subjective grading. In this model, we perform hormonal stimulation of donor mice, intraperitoneal injection, systematic abdominal survey and tissue harvest, and histologic quantification that can be performed and verified at any time after necropsy. This model requires minimal resources and training; does not require expertise by lab technicians in murine survival surgery or in the identification of gross endometriotic lesions; can be used in immunocompromised, immunocompetent, and/or mutant mice; and reliably creates endometriotic lesions that are histologically consistent with human endometriotic disease.
    Keywords animal models ; endometriosis ; endometrium ; histology ; humans ; intraperitoneal injection ; mice ; mutants ; necropsy ; pain ; surgery ; surveys
    Language English
    Dates of publication 2020-1124
    Size p. e61960.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/61960
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Insulin Sensitivity Is Retained in Mice with Endothelial Loss of Carcinoembryonic Antigen Cell Adhesion Molecule 1.

    Muturi, Harrison T / Khuder, Saja S / Ghadieh, Hilda E / Esakov, Emily L / Noh, Hyelim / Kang, Heejoon / McInerney, Marcia F / Kim, Jason K / Lee, Abraham D / Najjar, Sonia M

    Cells

    2021  Volume 10, Issue 8

    Abstract: CEACAM1 regulates endothelial barrier integrity. Because insulin signaling in extrahepatic target tissues is regulated by insulin transport through the endothelium, we aimed at investigating the metabolic role of endothelial CEACAM1. To this end, we ... ...

    Abstract CEACAM1 regulates endothelial barrier integrity. Because insulin signaling in extrahepatic target tissues is regulated by insulin transport through the endothelium, we aimed at investigating the metabolic role of endothelial CEACAM1. To this end, we generated endothelial cell-specific
    MeSH term(s) Adipocytes/metabolism ; Animals ; Carcinoembryonic Antigen/genetics ; Carcinoembryonic Antigen/metabolism ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Fats/metabolism ; Glucose/metabolism ; Inflammation ; Insulin/metabolism ; Insulin Resistance/genetics ; Liver/cytology ; Liver/metabolism ; Mice ; Mice, Knockout ; NF-kappa B/metabolism ; Nitric Oxide/metabolism ; Signal Transduction
    Chemical Substances Carcinoembryonic Antigen ; Ceacam1 protein, mouse ; Fats ; Insulin ; NF-kappa B ; Nitric Oxide (31C4KY9ESH) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2021-08-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10082093
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Therapeutic strategies to induce ERα in luminal breast cancer to enhance tamoxifen efficacy.

    Esakov, Emily L / Hale, James / Richards, Elliott G / Torre-Healy, Luke / Gullapalli, Keerthi / Trivedi, Div / Chumakova, Anastasia / Wessely, Oliver / Jensen, Jan / Lathia, Justin / Reizes, Ofer

    Endocrine-related cancer

    2019  Volume 26, Issue 8, Page(s) 689–698

    Abstract: Breast cancer is the most prevalent malignancy and second leading cause of death in women worldwide, with hormone receptor-positive luminal breast cancers being the most widespread subtype. While these tumors are generally amenable to endocrine therapy, ... ...

    Abstract Breast cancer is the most prevalent malignancy and second leading cause of death in women worldwide, with hormone receptor-positive luminal breast cancers being the most widespread subtype. While these tumors are generally amenable to endocrine therapy, cellular heterogeneity and acquired ability of tumor cells to undergo cell state switching makes these populations difficult to be fully targeted and eradicated through conventional methods. We have leveraged a quality-by-design (QbD) approach that integrates biological responses with predictive mathematical modeling to identify key combinations of commercially available drugs to induce estrogen receptor expression for therapeutic targeting. This technology utilizes a high level of automation through a custom-built platform to reduce bias as well as design-of-experiments methodology to minimize the experimental iterations required. Utilizing this approach, we identified a combination of clinical compounds, each at concentrations well below their efficacious dose, able to induce the expression of estrogen receptor alpha (ESR1) in hormone-positive breast cancer cells. Induction of ESR1 in luminal cells leads to chemosensitization. These findings provide proof of concept for the utility of the QbD strategy and identify a unique drug cocktail able to sensitize breast cancer cells to tamoxifen.
    MeSH term(s) Antineoplastic Agents, Hormonal/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm ; Estradiol/pharmacology ; Estrogen Receptor alpha/biosynthesis ; Estrogen Receptor alpha/metabolism ; Everolimus/administration & dosage ; Female ; Humans ; Hydroxamic Acids/administration & dosage ; Indazoles/administration & dosage ; MCF-7 Cells ; Paclitaxel/administration & dosage ; Sulfonamides/administration & dosage ; Tamoxifen/analogs & derivatives ; Tamoxifen/pharmacology ; Tumor Cells, Cultured
    Chemical Substances 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine ; Antineoplastic Agents, Hormonal ; Estrogen Receptor alpha ; Hydroxamic Acids ; Indazoles ; Sulfonamides ; Tamoxifen (094ZI81Y45) ; afimoxifene (17197F0KYM) ; Estradiol (4TI98Z838E) ; Everolimus (9HW64Q8G6G) ; belinostat (F4H96P17NZ) ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2019-06-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1218450-0
    ISSN 1479-6821 ; 1351-0088
    ISSN (online) 1479-6821
    ISSN 1351-0088
    DOI 10.1530/ERC-19-0042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Role for hepatic CEACAM1 in regulating fatty acid metabolism along the adipocyte-hepatocyte axis.

    Russo, Lucia / Ghadieh, Hilda E / Ghanem, Simona S / Al-Share, Qusai Y / Smiley, Zachary N / Gatto-Weis, Cara / Esakov, Emily L / McInerney, Marcia F / Heinrich, Garrett / Tong, Xin / Yin, Lei / Najjar, Sonia M

    Journal of lipid research

    2016  Volume 57, Issue 12, Page(s) 2163–2175

    Abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance and mediating suppression of fatty acid synthase activity. Feeding C57BL/6J male mice with a high-fat (HF) diet for 3- ...

    Abstract Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance and mediating suppression of fatty acid synthase activity. Feeding C57BL/6J male mice with a high-fat (HF) diet for 3-4 weeks triggered a >60% decrease in hepatic CEACAM1 levels to subsequently impair insulin clearance and cause systemic insulin resistance and hepatic steatosis. This study aimed at investigating whether lipolysis drives reduction in hepatic CEACAM1 and whether this constitutes a key mechanism leading to diet-induced metabolic abnormalities. Blocking lipolysis with a daily intraperitoneal injection of nicotinic acid in the last two days of a 30-day HF feeding regimen demonstrated that white adipose tissue (WAT)-derived fatty acids repressed hepatic CEACAM1-dependent regulation of insulin and lipid metabolism in 3-month-old male C57BL/6J mice. Adenoviral-mediated CEACAM1 redelivery countered the adverse metabolic effect of the HF diet on insulin resistance, hepatic steatosis, visceral obesity, and energy expenditure. It also reversed the effect of HF diet on inflammation and fibrosis in WAT and liver. This assigns a causative role for lipolysis-driven decrease in hepatic CEACAM1 level and its regulation of insulin and lipid metabolism in sustaining systemic insulin resistance, hepatic steatosis, and other abnormalities associated with excessive energy supply.
    MeSH term(s) Adipocytes/metabolism ; Adipose Tissue, White/drug effects ; Adipose Tissue, White/metabolism ; Adipose Tissue, White/pathology ; Animals ; Carcinoembryonic Antigen/physiology ; Cells, Cultured ; Diet, High-Fat/adverse effects ; Energy Metabolism ; Fatty Acids/metabolism ; Fibrosis ; Hepatocytes/metabolism ; Insulin Resistance ; Lipid Metabolism ; Male ; Mice, Inbred C57BL ; Niacin/pharmacology ; Obesity/etiology ; Obesity/metabolism
    Chemical Substances Carcinoembryonic Antigen ; Ceacam1 protein, mouse ; Fatty Acids ; Niacin (2679MF687A)
    Language English
    Publishing date 2016-10-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    DOI 10.1194/jlr.M072066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Hepatic CEACAM1 Over-Expression Protects Against Diet-Induced Fibrosis and Inflammation in White Adipose Tissue.

    Lester, Sumona G / Russo, Lucia / Ghanem, Simona S / Khuder, Saja S / DeAngelis, Anthony M / Esakov, Emily L / Bowman, Thomas A / Heinrich, Garrett / Al-Share, Qusai Y / McInerney, Marcia F / Philbrick, William M / Najjar, Sonia M

    Frontiers in endocrinology

    2015  Volume 6, Page(s) 116

    Abstract: CEACAM1 promotes insulin extraction, an event that occurs mainly in liver. Phenocopying global Ceacam1 null mice (Cc1(-/-) ), C57/BL6J mice fed a high-fat (HF) diet exhibited reduced hepatic CEACAM1 levels and impaired insulin clearance, followed by ... ...

    Abstract CEACAM1 promotes insulin extraction, an event that occurs mainly in liver. Phenocopying global Ceacam1 null mice (Cc1(-/-) ), C57/BL6J mice fed a high-fat (HF) diet exhibited reduced hepatic CEACAM1 levels and impaired insulin clearance, followed by hyperinsulinemia, insulin resistance, and visceral obesity. Conversely, forced liver-specific expression of CEACAM1 protected insulin sensitivity and energy expenditure, and limited gain in total fat mass by HF diet in L-CC1 mice. Because CEACAM1 protein is barely detectable in white adipose tissue (WAT), we herein investigated whether hepatic CEACAM1-dependent insulin clearance pathways regulate adipose tissue biology in response to dietary fat. While HF diet caused a similar body weight gain in L-CC1, this effect was delayed and less intense relative to wild-type (WT) mice. Histological examination revealed less expansion of adipocytes in L-CC1 than WT by HF intake. Immunofluorescence analysis demonstrated a more limited recruitment of crown-like structures, and qRT-PCR analysis showed no significant rise in TNFα mRNA levels in response to HF intake in L-CC1 than WT mice. Unlike WT, HF diet did not activate TGF-β in WAT of L-CC1 mice, as assessed by Western analysis of Smad2/3 phosphorylation. Consistently, HF diet caused relatively less collagen deposition in L-CC1 than WT mice, as shown by Trichrome staining. Coupled with reduced lipid redistribution from liver to visceral fat, lower inflammation and fibrosis could contribute to protected energy expenditure against HF diet in L-CC1 mice. The data underscore the important role of hepatic insulin clearance in the regulation of adipose tissue inflammation and fibrosis.
    Language English
    Publishing date 2015
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2015.00116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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