Browsing by Subject "Cholangiocarcinoma"

Now showing 1 - 10 of 19
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    A Unique Case of Caroli Disease in Kenya's Medical Landscape
    (International Scientific Information, 2024-01-12) Lengoiboni, Timothy Sanny; Kailani, Leway; Bikoro, Maureen K.; Mudeheri, Michael M.; Medicine, School of Medicine
    Background: If a young patient presents with fever, abdominal pain, jaundice and significant imaging abnormalities, especially dilation of the biliary system, it is usually due to obstruction from stones or strictures. However, on very rare occasions, it can be due to complications of congenital cystic dilatation of the biliary system, known as Caroli disease. We present such a patient and discuss the differential diagnosis and implications for long-term management. Case Report: A 14-year-old boy presented to the Emergency Department with a sudden onset of high-grade fever and abdominal pain for 2 weeks, accompanied by vomiting of blood. The patient had no relevant medical history. He was malnourished and had moderate pallor, jaundice, and right upper quadrant pain. Imaging revealed cystic dilatation of intrahepatic ducts and a central dot sign. There were no features suggesting advanced liver disease otherwise, and no tumors or cysts in the kidneys. A diagnosis of Caroli disease was made. The symptoms were ascribed to acute cholangitis and improved with antibiotics. He was discharged home 1 week later. No further blood loss was observed. Conclusions: This case study describes a patient with ascending cholangitis, a complication of Caroli disease. This diagnosis should be considered in the differential diagnosis when a child or young adult presents with features of cholangitis, abnormal biliary imaging, and/or upper gastrointestinal bleeding, or portal hypertension. No prior cases of this disease have been encountered, documented, or published in Kenya. This case can increase awareness among primary care clinicians, including pediatricians.
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    Addressing unmet needs for people with cancer cachexia: recommendations from a multistakeholder workshop
    (Wiley, 2022-04) Garcia, Jose M.; Dunne, Richard F.; Santiago, Kristen; Martin, Lisa; Birnbaum, Morris J.; Crawford, Jeffrey; Hendifar, Andrew E.; Kochanczyk, Martin; Moravek, Cassadie; Piccinin, Doris; Picozzi, Vincent; Roeland, Eric J.; Selig, Wendy K.D.; Zimmers, Teresa A.; Surgery, School of Medicine
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    Cholangiocarcinoma: bridging the translational gap from preclinical to clinical development and implications for future therapy
    (Taylor & Francis, 2021) Baiocchi, Leonardo; Sato, Keisaku; Ekser, Burcin; Kennedy, Lindsey; Francis, Heather; Ceci, Ludovica; Lenci, Ilaria; Alvaro, Domenico; Franchitto, Antonio; Onori, Paolo; Gaudio, Eugenio; Wu, Chaodong; Chakraborty, Sanjukta; Glaser, Shannon; Alpini, Gianfranco; Medicine, School of Medicine
    Introduction: Cholangiocarcinoma (CCA) is a devastating liver tumor with a poor prognosis. While less than 50% of patients with CCA may benefit from surgical resection, the rest undergoes chemotherapy with disappointing results (mean survival <2 years). Alternative pharmacological treatments are needed to improve the outcomes in patients with CCA. Areas covered: In this review, we discuss CCA-related: i) experimental systems used in preclinical studies; ii) pharmacological targets identified by genetic analysis; iii) results obtained in preliminary trials in human with their pros and cons; and iv) possible targeting of endocrinal modulation. A PubMed bibliographic search matching the term “cholangiocarcinoma” with “experimental model”, “preclinical model”, “genetic target”, “targeted therapy”, “clinical trial” or “translational research” was conducted and manuscripts published between 2010 and 2020 were retrieved for reading and reviewing. Expert opinion: Several factors contribute to the translational gap between bench research and clinical practice in CCA. The tumor heterogeneity, lack of a preclinical model recapitulating the different features of CCA, and difficult patient enrollment in clinical trials are elements to consider for basic and clinical research in CCA. Establishment of international networks formed by experts in the field of CCA may improve future research and its translational findings on patients.
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    Cholangiocarcinoma: novel therapeutic targets
    (Taylor & Francis, 2020-04) Sato, Keisaku; Glaser, Shannon; Alvaro, Domenico; Meng, Fanyin; Francis, Heather; Alpini, Gianfranco; Medicine, School of Medicine
    Introduction: Cholangiocarcinoma (CCA) is a liver cancer derived from the biliary tree with a less than 30% five-year survival rate. Early diagnosis of CCA is challenging and treatment options are limited. Some CCA patients have genetic mutations and several therapeutic drugs or antibodies have been introduced to target abnormally expressed proteins. However, CCA is heterogeneous and patients often present with drug resistance which is attributed to multiple mutations or other factors. Novel approaches and methodologies for CCA treatments are in demand.Area covered: This review summarizes current approaches for CCA treatments leading to the development of novel therapeutic drugs or tools for human CCA patients. A literature search was conducted in PubMed utilizing the combination of the searched term 'cholangiocarcinoma' with other keywords such as 'miRNA', 'FGFR', 'immunotherapy' or 'microenvironment'. Papers published within 2015-2019 were obtained for reading.Expert opinion: Preclinical studies have demonstrated promising therapeutic approaches that target various cells or pathways. Recent studies have revealed that hepatic cells coordinate to promote CCA tumor progression in the tumor microenvironment, which may be a new therapeutic target. Although further studies are required, novel therapeutic tools such as extracellular vesicles could be utilized to manage CCA and its microenvironment.
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    Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies
    (Frontiers Media, 2020-02) Sato, Keisaku; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco; Medicine, School of Medicine
    Long non-coding RNAs (lncRNAs) are RNAs with lengths exceeding 200 nucleotides that are not translated into proteins. It is well-known that small non-coding RNAs, such as microRNAs (miRNAs), regulate gene expression and play an important role in cholangiopathies. Recent studies have demonstrated that lncRNAs may also play a key role in the pathophysiology of cholangiopathies. Patients with cholangiopathies often develop cholangiocarcinoma (CCA), which is cholangiocyte-derived cancer, in the later stage. Cholangiocytes are a primary target of therapies for cholangiopathies and CCA development. Previous studies have demonstrated that expression levels of lncRNAs are altered in the liver of cholangiopathies or CCA tissues. Some lncRNAs regulate gene expression by inhibiting functions of miRNAs leading to diseased liver conditions or CCA progression, suggesting that lncRNAs could be a novel therapeutic target for those disorders. This review summarizes current understandings of functional roles of lncRNAs in cholangiopathies and seek their potentials for novel therapies.
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    Current Advances in Basic and Translational Research of Cholangiocarcinoma
    (MDPI, 2021-06-01) Sato, Keisaku; Baiocchi, Leonardo; Kennedy, Lindsey; Zhang, Wenjun; Ekser, Burcin; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco; Medicine, School of Medicine
    Cholangiocarcinoma (CCA) is a type of biliary tract cancer emerging from the biliary tree. CCA is the second most common primary liver cancer after hepatocellular carcinoma and is highly aggressive resulting in poor prognosis and patient survival. Treatment options for CCA patients are limited since early diagnosis is challenging, and the efficacy of chemotherapy or radiotherapy is also limited because CCA is a heterogeneous malignancy. Basic research is important for CCA to establish novel diagnostic testing and more effective therapies. Previous studies have introduced new techniques and methodologies for animal models, in vitro models, and biomarkers. Recent experimental strategies include patient-derived xenograft, syngeneic mouse models, and CCA organoids to mimic heterogeneous CCA characteristics of each patient or three-dimensional cellular architecture in vitro. Recent studies have identified various novel CCA biomarkers, especially non-coding RNAs that were associated with poor prognosis or metastases in CCA patients. This review summarizes current advances and limitations in basic and translational studies of CCA.
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    Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
    (MDPI, 2021-07-04) Baiocchi, Leonardo; Lenci, Ilaria; Milana, Martina; Kennedy, Lindsey; Sato, Keisaku; Zhang, Wenjun; Ekser, Burcin; Ceci, Ludovica; Meadows, Vik; Glaser, Shannon; Alpini, Gianfranco; Francis, Heather; Medicine, School of Medicine
    Cholangiocarcinoma is a lethal disease with scarce response to current systemic therapy. The rare occurrence and large heterogeneity of this cancer, together with poor knowledge of its molecular mechanisms, are elements contributing to the difficulties in finding an appropriate cure. Cholangiocytes (and their cellular precursors) are considered the liver component giving rise to cholangiocarcinoma. These cells respond to several hormones, neuropeptides and molecular stimuli employing the cAMP/PKA system for the translation of messages in the intracellular space. For instance, in physiological conditions, stimulation of the secretin receptor determines an increase of intracellular levels of cAMP, thus activating a series of molecular events, finally determining in bicarbonate-enriched choleresis. However, activation of the same receptor during cholangiocytes' injury promotes cellular growth again, using cAMP as the second messenger. Since several scientific pieces of evidence link cAMP signaling system to cholangiocytes' proliferation, the possible changes of this pathway during cancer growth also seem relevant. In this review, we summarize the current findings regarding the cAMP pathway and its role in biliary normal and neoplastic cell proliferation. Perspectives for targeting the cAMP machinery in cholangiocarcinoma therapy are also discussed.
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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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    Dual Role of Bile Acids on the Biliary Epithelium: Friend or Foe?
    (MDPI, 2019-04-16) Baiocchi, Leonardo; Zhou, Tianhao; Liangpunsakul, Suthat; Lenci, Ilaria; Santopaolo, Francesco; Meng, Fanyin; Kennedy, Lindsey; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco; Medicine, School of Medicine
    Bile acids are a family of amphipathic compounds predominantly known for their role in solubilizing and absorbing hydrophobic compounds (including liposoluble vitamins) in the intestine. Bile acids also are key signaling molecules and inflammatory agents that activate transcriptional factors and cell signaling pathways that regulate lipid, glucose, and energy metabolism in various human disorders, including chronic liver diseases. However, in the last decade increased awareness has been founded on the physiological and chemical heterogeneity of this category of compounds and their possible beneficial or injurious effects on the biliary tree. In this review, we provide an update on the current understanding of the molecular mechanism involving bile acid and biliary epithelium. The last achievements of the research in this field are summarized, focusing on the molecular aspects and the elements with relevance regarding human liver diseases.