Browsing by Subject "Bile duct neoplasms"

Now showing 1 - 5 of 5
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    Development and Characterization of Human Primary Cholangiocarcinoma Cell Lines
    (Elsevier, 2022) Isidan, Abdulkadir; Yenigun, Ali; Soma, Daiki; Aksu, Eric; Lopez, Kevin; Park, Yujin; Cross-Najafi, Arthur; Li, Ping; Kundu, Debjyoti; House, Michael G.; Chakraborty, Sanjukta; Glaser, Shannon; Kennedy, Lindsey; Francis, Heather; Zhang, Wenjun; Alpini, Gianfranco; Ekser, Burcin; Medicine, School of Medicine
    Cholangiocarcinoma (CCA) is the second most common primary liver tumor and is associated with late diagnosis, limited treatment options, and a 5-year survival rate of around 30%. CCA cell lines were first established in 1971, and since then, only 70 to 80 CCA cell lines have been established. These cell lines have been essential in basic and translational research to understand and identify novel mechanistic pathways, biomarkers, and disease-specific genes. Each CCA cell line has unique characteristics, reflecting a specific genotype, sex-related properties, and patient-related signatures, making them scientifically and commercially valuable. CCA cell lines are crucial in the use of novel technologies, such as three-dimensional organoid models, which help to model the tumor microenvironment and cell-to-cell crosstalk between tumor-neighboring cells. This review highlights crucial information on CCA cell lines, including: i) type of CCA (eg, intra- or extrahepatic), ii) isolation source (eg, primary tumor or xenograft), iii) chemical digestion method (eg, trypsin or collagenase), iv) cell-sorting method (colony isolation or removal of fibroblasts), v) maintenance-medium choice (eg, RPMI or Dulbecco's modified Eagle's medium), vi) cell morphology (eg, spindle or polygonal shape), and vii) doubling time of cells.
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    Doublecortin-Like Kinase Protein 1 in Cholangiocarcinoma: Is This the Biomarker and Target We Have Been Looking For?
    (Wolters Kluwer, 2021) Meadows, Vik; Francis, Heather; Medicine, School of Medicine
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    Organoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma
    (Wolters Kluwer, 2021) Sato, Keisaku; Zhang, Wenjun; Safarikia, Samira; Isidan, Abdulkadir; Chen, Angela M.; Li, Ping; Francis, Heather; Kennedy, Lindsey; Baiocchi, Leonardo; Alvaro, Domenico; Glaser, Shannon; Ekser, Burcin; Alpini, Gianfranco; Medicine, School of Medicine
    Cholangiopathies, such as primary sclerosing cholangitis, biliary atresia, and cholangiocarcinoma, have limited experimental models. Not only cholangiocytes but also other hepatic cells including hepatic stellate cells and macrophages are involved in the pathophysiology of cholangiopathies, and these hepatic cells orchestrate the coordinated response against diseased conditions. Classic two-dimensional monolayer cell cultures do not resemble intercellular cell-to-cell interaction and communication; however, three-dimensional cell culture systems, such as organoids and spheroids, can mimic cellular interaction and architecture between hepatic cells. Previous studies have demonstrated the generation of hepatic or biliary organoids/spheroids using various cell sources including pluripotent stem cells, hepatic progenitor cells, primary cells from liver biopsies, and immortalized cell lines. Gene manipulation, such as transfection and transduction can be performed in organoids, and established organoids have functional characteristics which can be suitable for drug screening. This review summarizes current methodologies for organoid/spheroid formation and a potential for three-dimensional hepatic cell cultures as in vitro models of cholangiopathies.
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    Targeting Lymphangiogenesis and Lymph Node Metastasis in Liver Cancer
    (Elsevier, 2021) Roy, Sukanya; Banerjee, Priyanka; Ekser, Burcin; Bayless, Kayla; Zawieja, David; Alpini, Gianfranco; Glaser, Shannon S.; Chakraborty, Sanjukta; Surgery, School of Medicine
    Increased lymphangiogenesis and lymph node metastasis, the important prognostic indicators of aggressive hepatobiliary malignancies such as hepatocellular cancer and cholangiocarcinoma, are associated with poor patient outcome. The liver produces 25% to 50% of total lymphatic fluid in the body and has a dense network of lymphatic vessels. The lymphatic system plays critical roles in fluid homeostasis and inflammation and immune response. Yet, lymphatic vessel alterations and function are grossly understudied in the context of liver pathology. Expansion of the lymphatic network has been documented in clinical samples of liver cancer; and although largely overlooked in the liver, tumor-induced lymphangiogenesis is an important player, increasing tumor metastasis in several cancers. This review aims to provide a detailed perspective on the current knowledge of alterations in the hepatic lymphatic system during liver malignancies, as well as various molecular signaling mechanisms and growth factors that may provide future targets for therapeutic intervention. In addition, the review also addresses current mechanisms and bottlenecks for effective therapeutic targeting of tumor-associated lymphangiogenesis.
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    The Functional Roles of Immune Cells in Primary Liver Cancer
    (Elsevier, 2022) Pham, Linh; Kyritsi, Konstantina; Zhou, Tianhao; Ceci, Ludovica; Baiocchi, Leonardo; Kennedy, Lindsey; Chakraborty, Sanjukta; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco; Sato, Keisaku; Medicine, School of Medicine
    Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Incidence of liver cancer has been increasing in recent years, and the 5-year survival is <20%. HCC and CCA are often accompanied with a dense stroma coupled with infiltrated immune cells, which is referred to as the tumor microenvironment. Populations of specific immune cells, such as high density of CD163+ macrophages and low density of CD8+ T cells, are associated with prognosis and survival rates in both HCC and CCA. Immune cells in the tumor microenvironment can be a therapeutic target for liver cancer treatments. Previous studies have introduced immunotherapy using immune checkpoint inhibitors, pulsed dendritic cells, or transduced T cells, to enhance cytotoxicity of immune cells and inhibit tumor growth. This review summarizes current understanding of the roles of immune cells in primary liver cancer covering HCC and CCA.