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https://www.readbyqxmd.com/read/28089783/characterization-of-rat-or-human-hepatocytes-cultured-in-microphysiological-systems-mps-to-identify-hepatotoxicity
#1
Shih-Yu Chang, Jenna L Voellinger, Kirk P Van Ness, Brian Chapron, Rachel M Shaffer, Thomas Neumann, Collin C White, Terrance J Kavanagh, Edward J Kelly, David L Eaton
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28052155/effect-of-background-liver-cirrhosis-on-outcomes-of-hepatectomy-for-hepatocellular-carcinoma
#2
Kazunari Sasaki, Junichi Shindoh, Georgios A Margonis, Yujiro Nishioka, Nikolaos Andreatos, Akinari Sekine, Masaji Hashimoto, Timothy M Pawlik
Importance: Background hepatocarcinogenesis is considered a major cause of postoperative recurrence of de novo hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). The degree of underlying liver injury has reportedly correlated with surgical outcomes of HCC. However, the pattern and annual rate of recurrence of postoperative de novo HCC are still unclear. Objective: To clarify the pattern and rate of recurrence of de novo HCC in patients with LC...
January 4, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/27979927/determination-of-aflatoxin-b1-lysine-in-pig-serum-and-plasma-by-liquid-chromatography-tandem-mass-spectrometry
#3
Mayra C Di Gregorio, Alessandra V Jager, Aline A Costa, Keliani Bordin, George E Rottinhghaus, Tânia Petta, Pollyana C M C Souto, Fabio E L Budiño, Carlos A F Oliveira
Aflatoxin B1 (AFB1) is a hepatocarcinogen produced by certain Aspergillus species growing on crops. After biotransformation in the liver, AFB1 generates several metabolites, one of which is AFB1 bound to lysine on serum albumin. AFB1-lysine (AFB1-lys) is a digest product of AFB1-albumin and is considered a biomarker of exposure to AFB1 in humans and animals. The objectives of this paper were to evaluate the performance characteristics of a new analytical method for determination of AFB1-lys levels in pig serum, heparinized and ethylenediaminetetraacetic acid (EDTA) plasma and to evaluate the interference of these anticoagulants in AFB1-lys quantification...
December 15, 2016: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/27924530/aspergillus-species-and-their-associated-mycotoxins
#4
Giancarlo Perrone, Antonia Gallo
The genus Aspergillus is among the most abundant and widely distributed organism on earth, and at the moment comprises 339 known species. It is one of the most important economically fungal genus and the biotechnological use of Aspergillus species is related to production of soy sauce, of different hydrolytic enzymes (amylases, lipases) and organic acid (citric acid, gluconic acid), as well as biologically active metabolites such as lovastatin. Although they are not considered to be major cause of plant diseases, Aspergillus species are responsible for several disorders in various plants and plant products, especially as opportunistic storage moulds...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914986/identification-of-epigenetically-downregulated-tmem70-and-ube2e2-in-rat-liver-after-28-day-treatment-with-hepatocarcinogenic-thioacetamide-showing-gene-product-downregulation-in-hepatocellular-preneoplastic-and-neoplastic-lesions-produced-by-tumor-promotion
#5
Sayaka Mizukami, Atsunori Yafune, Yousuke Watanabe, Kota Nakajima, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
The present study identified genes showing promoter region hypermethylation by CpG island microarrays in the liver of rats treated with hepatocarcinogen thioacetamide (TAA) for 28days. Among 47 hypermethylated genes, Hist1h2aa, Tmem70, Ube2e2, and Slk were confirmed to show hypermethylation by methylation-specific quantitative polymerase chain reaction (PCR) and pyrosequencing analyses as well as downregulation of transcript levels by real-time reverse transcription-PCR analysis in the livers of rats treated with TAA...
January 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27914868/determination-of-aflatoxin-m1-in-urine-samples-indicates-frequent-dietary-exposure-to-aflatoxin-b1-in-the-bangladeshi-population
#6
Nurshad Ali, Meinolf Blaszkewicz, Khaled Hossain, Gisela H Degen
Aflatoxin B1 (AFB1), a hepatocarcinogen and highly toxic mycotoxin, is a contaminant of food commodities, especially in hot and humid climates that favour the growth of aflatoxin-producing fungi. As data on AFB1 contamination of food and feed in Bangladesh are scarce, we conducted an initial screening by ELISA on the occurrence of the metabolite and biomarker aflatoxin M1 (AFM1) in urines from Bangladesh which indicated frequent exposure. This finding led us to conduct a follow-up study where we applied a more sensitive method (IAC clean-up and HPLC-FD analysis) to determine AFM1 concentrations in a larger set of urine samples...
November 10, 2016: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/27878498/stimulation-of-diethylnitrosamine-metabolism-reduces-its-general-toxic-and-hepatocarcinogenic-effects
#7
S I Il'nitskaya, V I Kaledin, L A Bogdanova, T S Morozkova, V I Kapustina, M L Perepechaeva, A Yu Grishanova
The general toxic and hepatocarcinogenic effects of diethylnitrosamine after stimulation of its metabolism with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP) were studied. The hydroxylating activity of liver microsomes of C57Bl/6Mv mice towards p-nitrophenol increased more than 4-fold 3 days after injection of TCPOBOP. Injection of diethylnitrosamine 3 days after TCPOBOP caused a lesser body weight loss and decrease of food consumption in C57Bl/6Mv mice than in response to diethylnitrosamine without preinduction...
November 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27871980/low-dose-assessment-of-the-carcinogenicity-of-furan-in-male-f344-n-nctr-rats-in-a-2-year-gavage-study
#8
Linda S Von Tungeln, Nigel J Walker, Greg R Olson, Maria C B Mendoza, Robert P Felton, Brett T Thorn, M Matilde Marques, Igor P Pogribny, Daniel R Doerge, Frederick A Beland
Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0...
January 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27832320/activation-of-nuclear-receptor-car-by-an-environmental-pollutant-perfluorooctanoic-acid
#9
Taiki Abe, Mirei Takahashi, Makoto Kano, Yuto Amaike, Chizuru Ishii, Kazuhiro Maeda, Yuki Kudoh, Toru Morishita, Takuomi Hosaka, Takamitsu Sasaki, Susumu Kodama, Atsushi Matsuzawa, Hiroyuki Kojima, Kouichi Yoshinari
Perfluorocarboxylic acids (PFCAs) including perfluorooctanoic acid (PFOA) are environmental pollutants showing high accumulation, thermochemical stability and hepatocarcinogenicity. Peroxisome proliferator-activated receptor α is suggested to mediate their toxicities, but the precise mechanism remains unclear. Previous reports also imply a possible role of constitutive androstane receptor (CAR), a key transcription factor for the xenobiotic-induced expression of various genes involved in drug metabolism and disposition as well as hepatocarcinogenesis...
November 10, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27825936/new-insights-into-the-molecular-mechanisms-of-chemical-carcinogenesis-in-vivo-adduction-of-histone-h2b-by-a-reactive-metabolite-of-the-chemical-carcinogen-furan
#10
João Nunes, Inês L Martins, Catarina Charneira, Igor P Pogribny, Aline de Conti, Frederick A Beland, M Matilde Marques, Cristina C Jacob, Alexandra M M Antunes
Furan is a rodent hepatocarcinogen ubiquitously found in the environment and heat-processed foods. Furan undergoes cytochrome P450 2E1-catalyzed bioactivation to cis-2-butene-1,4-dial (BDA), which has been shown to form an electrophilic conjugate (GSH-BDA) with glutathione. Both BDA and GSH-BDA yield covalent adducts with lysine residues in proteins. Dose- and time-dependent epigenetic histone alterations have been observed in furan-treated rats. While the covalent modification of histones by chemical carcinogens has long been proposed, histone-carcinogen adducts have eluded detection in vivo...
December 15, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27818125/aflatoxin-b1-disrupts-transient-receptor-potential-channel-activity-and-increases-cox-2-expression-in-jeg-3-placental-cells
#11
Yun Zhu, Yan Qin Tan, Lai K Leung
Aflatoxins are fungal metabolites which pose a major threat to food safety. Although these mycotoxins are established hepatocarcinogens, their effect on the reproductive organ is unknown. Transient Receptor Potential Channels (TRPs) are ubiquitously expressed in human tissues, including the placenta. These channels are associated with various functions in the placenta. The fetus and the placenta are especially sensitive to xenobiotic assault; therefore, exposure to the aflatoxins during gestation might lead to the undesirable outcome...
December 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27815472/in-vitro-proinflammatory-polarization-of-macrophages-isolated-from-hepatocarcinogenic-stage-in-humans-and-rats
#12
Marta Wójcik, Joanna Wessely-Szponder, Halina Cichoż-Lach, Krzysztof Celiński, Ryszard Bobowiec
Macrophages have multiple functions in both inhibiting and promoting hepatocarcinogenesis, which are dependent on their phenotypes. Thus, we were interested in clarifying the 'training' proinflammatory effects exerted by barley β-glucan (BBG) on monocyte-derived macrophages from patients with hepatocellular carcinoma (HCC-Mfs). After isolation and differentiation HCC-Mfs were treated with different concentrations of BBG and functional assays were then conducted after 24 h, and 3 and 5 days of incubation. The release of reactive oxygen species, arginase concentration and cell morphology were analyzed...
November 2016: In Vivo
https://www.readbyqxmd.com/read/27791012/notch3-drives-development-and-progression-of-cholangiocarcinoma
#13
Rachel V Guest, Luke Boulter, Benjamin J Dwyer, Timothy J Kendall, Tak-Yung Man, Sarah E Minnis-Lyons, Wei-Yu Lu, Andrew J Robson, Sofia Ferreira Gonzalez, Alexander Raven, Davina Wojtacha, Jennifer P Morton, Mina Komuta, Tania Roskams, Stephen J Wigmore, Owen J Sansom, Stuart J Forbes
The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27722163/hcc-associated-liver-transplantation-where-are-the-limits-and-what-are-the-new-regulations
#14
REVIEW
Christian P Strassburg
BACKGROUND: Hepatocellular carcinoma (HCC) represents an increasing health burden worldwide and a challenging disease both in terms of diagnosis and treatment. METHODS: The literature available on PubMed for the period of 1990-2016 was reviewed with reference to liver allocation, HCC, liver transplantation (LT), and prediction, and the allocation rules of the German Transplant Act were reviewed. RESULTS: Due to etiological and geographical diversity, HCC is not a homogeneous disease...
August 2016: Visceral Medicine
https://www.readbyqxmd.com/read/27713163/premalignant-alteration-assessment-in-liver-like-tissue-derived-from-embryonic-stem-cells-by-aristolochic-acid-i-exposure
#15
Tong Li, Ke Jin, Dan-Yan Zhu, Lu Li, Zheng Rong Mao, Bo Wen Wu, Yi Fan Wang, Zong Fu Pan, Lan Juan Li, Chun Sheng Xiang, Kun Kai Su, Yi Jia Lou
The in vitro predictive evaluation of chemical carcinogenicity based on hepatic premalignance has so far not been established. Here, we report a novel approach to investigate the premalignant events triggered by human carcinogen aristolochic acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6 phenotypic characteristics. Hepatocytes expressed STAT3/p-STAT3, c-Myc and Lin28B in parallel. Some of them displayed the dedifferentiation characteristics, such as full of α-fetoprotein granules, increase in size, and nucleocytoplasmic shuttle of Oct4...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27672403/dietary-broccoli-protects-against-fatty-liver-development-but-not-against-progression-of-liver-cancer-in-mice-pretreated-with-diethylnitrosamine
#16
Yung-Ju Chen, Angela D Myracle, Matthew A Wallig, Elizabeth H Jeffery
Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months...
June 2016: Journal of Functional Foods
https://www.readbyqxmd.com/read/27647242/the-aspergillus-flavus-flup-associated-metabolite-promotes-sclerotial-production
#17
Perng-Kuang Chang, Leslie L Scharfenstein, Kenneth C Ehrlich, José Diana Di Mavungu
Aspergillus flavus is able to synthesize a variety of polyketide-derived secondary metabolites including the hepatocarcinogen, aflatoxin B1. The fungus reproduces and disseminates predominantly by production of conidia. It also produces hardened mycelial aggregates called sclerotia that are used to cope with unfavourable growth environments. In the present study, we examined the role of A. flavus fluP, the backbone polyketide synthase gene of secondary metabolite gene cluster 41, on fungal development. The A...
October 2016: Fungal Biology
https://www.readbyqxmd.com/read/27547913/concurrent-fatty-liver-increases-risk-of-hepatocellular-carcinoma-among-patients-with-chronic-hepatitis-b
#18
Anthony W H Chan, Grace L H Wong, Hoi-Yun Chan, Joanna H M Tong, Yau-Hei Yu, Paul C L Choi, Henry L Y Chan, Ka-Fai To, Vincent W S Wong
BACKGROUND & AIMS: Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem due to the non-alcoholic fatty liver disease (NAFLD) pandemic. Concomitant obesity and diabetes increase the risk of HBV-related hepatocellular carcinoma (HCC) development. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically-proven fatty liver in HBV hepatocarcinogenesis...
August 22, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27542244/the-mitochondrial-and-endoplasmic-reticulum-pathways-involved-in-the-apoptosis-of-bursa-of-fabricius-cells-in-broilers-exposed-to-dietary-aflatoxin-b1
#19
Shibin Yuan, Bangyuan Wu, Zhengqiang Yu, Jing Fang, Na Liang, Mingqiang Zhou, Cheng Huang, Xi Peng
Aflatoxin B1 (AFB1), a toxic metabolite produced by some fungi, exerts well-known hepatocarcinogenic and immunosuppressive effects, the latter can increase the apoptotic immune cells in vitro. However, it is largely unknown that which signaling pathways contribute to excessive apoptosis of immune cells which induced by AFB1. In this study, we investigated the roles of the mitochondria, endoplasmic reticulum (ER) and death receptor activated apoptotic pathways in the bursal of Fabricius (BF) cells in the broilers exposed to AFB1 diet...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27511028/emodin-loaded-plga-tpgs-nanoparticles-combined-with-heparin-sodium-loaded-plga-tpgs-nanoparticles-to-enhance-chemotherapeutic-efficacy-against-liver-cancer
#20
Hongyan Liu, Hong Xu, Chenghong Zhang, Meng Gao, Xiaoguang Gao, Chuchu Ma, Li Lv, Dongyan Gao, Sa Deng, Changyuan Wang, Yan Tian
PURPOSE: Heparin sodium (HS)-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs) were prepared as a sustained and targeting delivery carrier and combined with emodin (EMO)-loaded PLGA-TPGS nanoparticles (EPTNs), which were investigated previously to form a combination therapy system for the treatment of liver cancer. METHODS: To assess cellular uptake and evaluate the liver-targeting capacity by analyzing the drug concentrations and frozen slices, HS/eosin-loaded PLGA-TPGS nanoparticles, HS/fluorescein- loaded PLGA-TPGS nanoparticles and EMO/C6-loaded PLGA-TPGS nanoparticles, which contained eosin, fluorescein and C6 as fluorescent probes, respectively, were also prepared...
November 2016: Pharmaceutical Research
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