Search results for "Hepatocellular Carcinoma"
showing 10 items of 702 documents
Ginkgo biloba induces different gene expression signatures and oncogenic pathways in malignant and non-malignant cells of the liver
2018
Ginkgo biloba (EGb761) is a widely used botanical drug. Several reports indicate that EGb761 confers preventive as well as anti-tumorigenic properties in a variety of tumors, including hepatocellular carcinoma (HCC). We here evaluate functional effects and molecular alterations induced by EGb761 in hepatoma cells and non-malignant hepatocytes. Hepatoma cell lines, primary human HCC cells and immortalized human hepatocytes (IH) were exposed to various concentrations (0-1000 μg/ml) of EGb761. Apoptosis and proliferation were evaluated after 72h of EGb761 exposure. Response to oxidative stress, tumorigenic properties and molecular changes were further investigated. While anti-oxidant effects w…
Cytotoxic effects induced by patulin, deoxynivalenol and toxin T2 individually and in combination in hepatic cells (HepG2).
2018
Abstract Patulin (PAT), deoxynivalenol (DON) and toxin T-2 (T-2) are mycotoxins distributed worldwide in food and feed. Cytotoxicity of the three mycotoxins individually or in combination in human hepatocellular carcinoma (HepG2) cells was evaluated by MTT assay over 24, 48 and 72 h of exposure. The concentration ranges used were 0.625–15 μM for DON, 1.25–50 nM for T-2 and 0.45–7.5 μM for PAT. The IC 50 values obtained ranged from 9.30 to 2.53 μM, from 33.69 to 44.37 nM and from 2.66 to 1.17 μM for DON, T-2 and PAT, respectively. The most cytotoxic mycotoxin to HepG2 cells was T-2 followed by PAT and DON. The combination ratios used for the mixtures were 1:3 (DON: T-2), 1:5 (DON: PAT), 1:1.…
Chemical Composition, In Vitro Antitumor and Pro-Oxidant Activities of Glandora rosmarinifolia (Boraginaceae) Essential Oil
2018
The biological properties of essential oils have been demonstrated in the treatment of several diseases and to enhance the bioavailability of other drugs. In natural habitats the essential oils compounds may play important roles in the protection of the plants as antibacterials, antivirals, antifungals, insecticides and also against herbivores by reducing their appetite for such plants or by repelling undesirable others. We analyzed by gas-chromatography mass spectrometry the chemical composition of the essential oil of aerial parts of Glandora rosmarinifolia (Ten.) D.C. Thomas obtained by hydrodistillation and verified some biological activities on a panel of hepatocellular carcinoma cell …
Prevention of endpoints in primary biliary cholangitis with ursodeoxycholic acid: quantifying the benefit
2020
Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with an established benefit for patients suffering from primary biliary cholangitis (PBC). It was first introduced in the 60s and took until the late 90s to demonstrate a survival benefit in large meta-cohort studies.1 Since then, UDCA is the established first-line therapy according to current guidelines.2 The benefit of UDCA is multidimensional, and patients receiving UDCA experience increased transplant-free survival, a decreased risk of hepatocellular carcinoma and potentially improved quality of life.3–5 The survival benefit is predicted by a number biochemical markers that reflect cholestasis and that are accepted surrogates of the…
Copper/MYC/CTR1 interplay: A dangerous relationship in hepatocellular carcinoma
2018
Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the prog…
Dual proteotoxic stress accelerates liver injury via activation of p62‐Nrf2
2021
Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and H…
Loss of organic cation transporter 3 (Oct3) leads to enhanced proliferation and hepatocarcinogenesis
2017
// Johanna Vollmar 1 , Anja Lautem 2 , Ellen Closs 3 , Detlef Schuppan 4 , Yong Ook Kim 4 , Daniel Grimm 1 , Jens U. Marquardt 1 , Peter Fuchs 1 , Beate K. Straub 5 , Arno Schad 5 , Dirk Grundemann 6 , Jorn M. Schattenberg 1 , Nadine Gehrke 1 , Marcus A. Worns 1 , Jan Baumgart 7 , Peter R. Galle 1 and Tim Zimmermann 1 1 Department of Internal Medicine, Gastroenterology and Hepatology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 2 Department of Hepatobiliary and Transplantation Surgery, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 3 Department of Pharmacology, University Medical Center, Johannes Gutenberg-University Mainz, …
A dual role of caspase-8 in triggering and sensing proliferation-associated DNA damage, a key determinant of liver cancer development.
2017
Summary Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apop…
Molecular targets in inhibition of hepatitis C virus replication
1997
Hepatitis C virus (HCV) is the major cause of transfusion-associated hepatitis and accounts for a significant proportion of hepatitis cases worldwide. Most, if not all, infections become persistent and about 60% of cases develop chronic liver disease with various outcomes ranging from an asymptomatic carrier state to chronic active hepatitis and liver cirrhosis, which is strongly associated with the development of hepatocellular carcinoma. Since the initial cloning of the viral genome in 1989, our knowledge of the molecular biology of HCV has increased rapidly and led to the identification of several potential targets for antiviral intervention. In contrast, the low replication of the virus…
Molecular bases of the poor response of liver cancer to chemotherapy
2018
Summary A characteristic shared by most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in adults, and in a lesser extent hepatoblastoma (HB) mainly in children, is their high refractoriness to chemotherapy. This is the result of synergic interactions among complex and diverse mechanisms of chemoresistance (MOC) in which more than 100 genes are involved. Pharmacological treatment, although it can be initially effective, frequently stimulates the expression of MOC genes, which results in the relapse of the tumor, usually with a more aggressive and less chemosensitive phenotype. Identification of the MOC genetic signature accounting fo…