Browsing by Author "Milana, Martina"

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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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    Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development
    (MDPI, 2022) Ceci, Ludovica; Zhou, Tianhao; Lenci, Ilaria; Meadows, Vik; Kennedy, Lindsey; Li, Ping; Ekser, Burcin; Milana, Martina; Zhang, Wenjun; Wu, Chaodong; Sato, Keisaku; Chakraborty, Sanjukta; Glaser, Shannon S.; Francis, Heather; Alpini, Gianfranco; Baiocchi, Leonardo; Medicine, School of Medicine
    The poor prognosis of cholangiocarcinoma in humans is related to several factors, such as (i) the heterogeneity of the disease, (ii) the late onset of symptoms and (iii) the limited comprehension of the carcinogenic pathways determining neoplastic changes, which all limit the pursuit of appropriate treatment. Several risk factors have been recognized, including different infective, immune-mediated, and dysmorphogenic disorders of the biliary tree. In this review, we report the details of possible mechanisms that lead a specific premalignant pathological condition to become cholangiocarcinoma. For instance, during liver fluke infection, factors secreted from the worms may play a major role in pathogenesis. In primary sclerosing cholangitis, deregulation of histamine and bile-acid signaling may determine important changes in cellular pathways. The study of these molecular events may also shed some light on the pathogenesis of sporadic (unrelated to risk factors) forms of cholangiocarcinoma, which represent the majority (nearly 75%) of cases.
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    Possible application of melatonin treatment in human diseases of the biliary tract
    (American Physiological Society, 2019-11) Baiocchi, Leonardo; Zhou, Tianhao; Liangpunsakul, Suthat; Ilaria, Lenci; Milana, Martina; Meng, Fanyin; Kennedy, Lindsey; Kusumanchi, Praveen; Yang, Zhihong; Ceci, Ludovica; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco; Medicine, School of Medicine
    Melatonin was discovered in 1958 by Aaron Lerner. Its name comes from the ability of melatonin to change the shape of amphibian melanophores from stellate to roundish. Starting from the 1980s, the role of melatonin in the regulation of mammalian circadian and seasonal clocks has been elucidated. Presently, several other effects have been identified in different organs. For example, the beneficial effects of melatonin in models of liver damage have been described. This review gives first a general background on experimental and clinical data on the use of melatonin in liver damage. The second part of the review focuses on the findings related to the role of melatonin in biliary functions, suggesting a possible use of melatonin therapy in human diseases of the biliary tree.