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https://www.readbyqxmd.com/read/28932315/experimental-hepatic-carcinogenesis-oxidative-stress-and-natural-antioxidants
#1
REVIEW
Velid Unsal, Ergül Belge-Kurutaş
Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C). Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN) mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons...
August 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#2
Eunüs S Ali, Grigori Y Rychkov, Greg J Barritt
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca(2+) in the lumen of the ER. In steatotic hepatocytes, store-operated Ca(2+) entry (SOCE) is substantially inhibited...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900384/cancer-chemoprevention-by-oleaster-elaeagnus-angustifoli-l-fruit-extract-in-a-model-of-hepatocellular-carcinoma-induced-by-diethylnitrosamine-in-rats
#3
Zahra Amereh, Nasrin Hatami, Farshad H Shirazi, Saman Gholami, Seyed Hojjat Hosseini, Maryam Noubarani, Mohammad Kamalinejad, Sina Andalib, Fariborz Keyhanfar, Mohammad Reza Eskandari
Hepatocellular carcinoma (HCC) is a frequent and fatal human cancer with poor diagnosis that accounts for over half a million deaths each year worldwide. Elaeagnus angustifolia L. known as oleaster has a wide range of pharmacological activities. This study aimed to investigate the chemopreventive effect of aqueous extract of E. angustifolia fruit (AEA) against diethylnitrosamine (DEN)-induced HCC in rats. HCC was induced in rats by a single injection of DEN (200 mg/kg) as an initiator. After two weeks, rats were orally administered 2-acetylaminofluorene or 2-AAF (30 mg/kg) as a promoter for two weeks...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28893626/low-density-lipoprotein-docosahexaenoic-acid-nanoparticles-induce-ferroptotic-cell-death-in-hepatocellular-carcinoma
#4
Weijun Ou, Rohit S Mulik, Arnida Anwar, Jeffrey G McDonald, Xiaoshun He, Ian R Corbin
Low-density lipoprotein nanoparticles reconstituted with the natural omega-3 fatty acid, docosahexaenoic acid (LDL-DHA), have been reported to selectively kill hepatoma cells and reduce the growth of orthotopic liver tumors in the rat. To date, little is known about the cell death pathways by which LDL-DHA nanoparticles kill tumor cells. Here we show that the LDL-DHA nanoparticles are cytotoxic to both rat hepatoma and human hepatocellular carcinoma (HCC) cell lines. Following LDL-DHA treatment both rat and human HCC cells experience pronounced lipid peroxidation, depletion of glutathione and inactivation of the lipid antioxidant glutathione peroxidase-4 (GPX4) prior to cell death...
September 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28885731/a-multifunctional-nanocarrier-for-efficient-trail-based-gene-therapy-against-hepatocellular-carcinoma-with-desmoplasia
#5
Chun-Hung Liu, Guann-Gen Chern, Fu-Fei Hsu, Kuan-Wei Huang, Yun-Chieh Sung, Hsi-Chien Huang, Jiantai Timothy Qiu, Sheng-Kai Wang, Chu-Chi Lin, Chien-Hsun Wu, Han-Chung Wu, Jia-Yu Liu, Yunching Chen
The anti-cancer efficacy of TNF-related apoptosis-inducing ligand (TRAIL)-based therapy is limited due to systemic toxicity, poor bioavailability, and the development of TRAIL-resistance. We developed a tumor-targeted LCPP (Lipid/Calcium/Phosphate/Protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells. TRAIL pDNA was encapsulated in a pH stimuli-responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, the intracellular release of Ca(2+) from the CaP core overcame TRAIL resistance via calcium influx-dependent DR5 upregulation...
September 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28876464/novel-mutations-in-transthyretin-gene-associated-with-hepatocellular-carcinoma
#6
Deepshikha Pande Katare, Shabnam Malik, Ruchi Jakhmola Mani, Maryam Ranjpour, S K Jain
Hepatocellular carcinoma (HCC) is one of the major health problems with increasing incidence worldwide. We report the elevation in transthyretin (TTR) expression following HCC induction using diethylnitrosamine (DEN) and 2-aminoacetylfluorine (2-AAF) in male Wistar rats. The increase in its expression took place at very early stage and remained elevated throughout HCC progression. The analysis of TTR gene in HCC bearing rats revealed four novel mutations that alter three amino acids at positions 61, 100 and 115...
September 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28874443/amelioration-of-diet-induced-steatohepatitis-in-mice-following-combined-therapy-with-aso-fsp27-and-fenofibrate
#7
Ananthi Rajamoorthi, Noemi Arias, Jeannine Basta, Richard G Lee, Ángel Baldán
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD progresses from benign steatosis to steatohepatitis (NASH) to cirrhosis, and is linked to hepatocellular carcinoma. No targeted treatment is currently approved for NAFLD/NASH. We showed that fat-specific protein 27 (FSP27), a lipid droplet-associated protein that controls triglyceride turnover in the hepatocyte, is required for fasting- and diet-induced triglyceride accumulation in the liver. However, silencing Fsp27 with antisense oligonucleotides (ASOs) did not improve hepatosteatosis in genetic nor nutritional mouse models of obesity...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28863318/therapeutic-effect-of-carnosine-in-rat-model-of-experimental-liver-carcinogenesis
#8
Amr A Fouad, Hatem O Qutub, Abdullatif S Al Rashed, Walid N Al-Melhim
The possible anticancer effect of carnosine versus doxorubicin was investigated against hepatocellular carcinoma (HCC) induced by trichloroacetic acid (TCA) (500mg/kg/day, p.o., for 5days) in rats. Following induction of HCC, rats treated with either carnosine (10mg/kg/day, i.p.), or doxorubicin (2.5mg/kg, i.p., once weekly), for 2 weeks. Carnosine significantly decreased serum alanine aminotransferase, and hepatic lipid peroxidation, nitric oxide, tumor necrosis factor-α, and nuclear factor-κB p65 unit, and significantly increased liver total antioxidant status in TCA-challenged rats...
August 26, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28862649/immune-evasion-strategies-during-chronic-hepatitis-b-and-c-virus-infection
#9
REVIEW
Ana Maria Ortega-Prieto, Marcus Dorner
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a major global healthcare problem with more than 240 million and 70 million infected, respectively. Both viruses persist within the liver and result in progressive liver disease, resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma. Strikingly, this pathogenesis is largely driven by immune responses, unable to clear an established infection, rather than by the viral pathogens themselves. Even though disease progression is very similar in both infections, HBV and HCV have evolved distinct mechanisms, by which they ensure persistence within the host...
September 1, 2017: Vaccines
https://www.readbyqxmd.com/read/28857485/non-alcoholic-fatty-liver-disease-promotes-hepatocellular-carcinoma-through-direct-and-indirect-effects-on-hepatocytes
#10
REVIEW
Chi Ma, Qianfei Zhang, Tim F Greten
Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasm and the second leading cause of cancer-related deaths worldwide. Non-alcoholic fatty liver disease (NAFLD), a common disorder in obese people, has been identified as an important risk factor for HCC. Following the increasing prevalence of obesity, it is expected that the contribution of NAFLD to HCC's incidence worldwide will grow. Recently, a number of studies have been published, which help us better understand cellular and molecular mechanisms of how NAFLD promotes hepatocarcinogensis...
August 31, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28854340/sequential-analysis-and-staging-of-a-diethylnitrosamine-induced-hepatocellular-carcinoma-in-male-wistar-albino-rat-model
#11
Abdallah H Fathy, Mohamad Abdel-Monem Bashandy, Samir Ae Bashandy, Ahmed M Mansour, Bakheet Mohammed Elsadek
Hepatocellular carcinoma (HCC) is one of the most life-threatening cancers. The present study was designed to chronologically analyze the HCC chemically induced by diethylnitrosamine (DEN) in male Wistar rats during 27 weeks. DEN was given to rats in drinking water (100 mg/L) to induce HCC. In the present study, the DEN administered groups recorded dramatic results in the tumor markers, oxidative stress, lipid profile, liver function and hematological parameters at all intervals when compared to their corresponding values in the control groups...
August 30, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28843857/anti-tumor-activity-of-kntc2-sirna-in-orthotopic-tumor-model-mice-of-hepatocellular-carcinoma
#12
Yukimasa Makita, Shumpei Murata, Yoshiki Katou, Kuniko Kikuchi, Hiroshi Uejima, Mika Teratani, Yasutaka Hoashi, Eriya Kenjou, Satoru Matsumoto, Masahiro Nogami, Kentaro Otake, Yuji Kawamata
Hepatocellular carcinoma (HCC) is still one of the major causes of cancer-related death. Kinetochore-associated protein 2 (KNTC2) is specifically upregulated in tumor tissues of HCC patients and recognized as a potential candidate target for the treatment of HCC. However, the relationship between KNTC2 and in vivo tumor growth of HCC is not yet fully understood. Here we encapsulated KNTC2 siRNAs into a lipid nanoparticle (LNP) and investigated their knockdown activity, target engagement marker, anti-tumor activity and hepatotoxicity in an orthotopic HCC model mice of Hep3B-luc cells...
August 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28840186/identification-of-the-consistently-altered-metabolic-targets-in-human-hepatocellular-carcinoma
#13
Zeribe Chike Nwosu, Dominik Andre Megger, Seddik Hammad, Barbara Sitek, Stephanie Roessler, Matthias Philip Ebert, Christoph Meyer, Steven Dooley
BACKGROUND & AIMS: Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC). METHODS: We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated...
September 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28830415/anti-cancer-effects-of-ajwa-dates-phoenix-dactylifera-l-in-diethylnitrosamine-induced-hepatocellular-carcinoma-in-wistar-rats
#14
Fazal Khan, Tariq Jamal Khan, Gauthaman Kalamegam, Peter Natesan Pushparaj, Adeel Chaudhary, Adel Abuzenadah, Taha Kumosani, Elie Barbour, Mohammed Al-Qahtani
BACKGROUND: Hepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer...
August 22, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28820612/the-potential-of-signal-peptide-peptidase-as-a-therapeutic-target-for-hepatitis-c
#15
REVIEW
Kohji Moriishi
Chronic infection with hepatitis C virus (HCV) causes liver steatosis, cirrhosis, metabolic syndrome with inflammation, and eventually leads to hepatocellular carcinoma. HCV core protein is a well-known capsid protein and pathogenic factor related to lipid accumulation, type 2 diabetes mellitus, and carcinogenesis. Cleavage of the C-terminal transmembrane region by signal peptide peptidase (SPP) is required for maturation of the core protein. Areas covered: Herein, this review details the general aspects of the structure, lifecycle, pathogenesis, and maturation of the HCV core protein, the function of SPP, and clinically available direct-acting antivirals (DAAs)...
September 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#16
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807240/role-of-exosomes-in-treatment-of-hepatocellular-carcinoma
#17
REVIEW
Demetrios Moris, Eliza W Beal, Jeffery Chakedis, Richard A Burkhart, Carl Schmidt, Mary Dillhoff, Xufeng Zhang, Stamatios Theocharis, Timothy M Pawlik
Exosomes are nanovesicles that may play a role in intercellular communication by acting as carriers of functional contents such as proteins, lipids, RNA molecules and circulating DNA from donor to recipient cells. In addition, exosomes may play a potential role in immunosurveillance and tumor pathogenesis and progression. Recently, research has increasingly focused on the role of exosomes in hepatocellular carcinoma (HCC), the most common primary liver malignancy. We herein review data on emerging experimental and clinical studies focused on the role of exosomes in the pathogenesis, diagnosis, progression and chemotherapy response of patients with HCC...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28802563/metabolic-circuit-involving-free-fatty-acids-microrna-122-and-triglyceride-synthesis-in-liver-and-muscle-tissues
#18
Chofit Chai, Mila Rivkin, Liav Berkovits, Alina Simerzin, Elina Zorde-Khvalevsky, Nofar Rosenberg, Shiri Klein, Dayana Yaish, Ronen Durst, Shoshana Shpitzen, Shiran Udi, Joseph Tam, Joerg Heeren, Anna Worthmann, Christoph Schramm, Johannes Kluwe, Revital Ravid, Eran Hornstein, Hilla Giladi, Eithan Galun
BACKGROUND & AIMS: Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. METHODS: We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines...
August 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28769563/delivery-of-mir-375-and-doxorubicin-hydrochloride-by-lipid-coated-hollow-mesoporous-silica-nanoparticles-to-overcome-multiple-drug-resistance-in-hepatocellular-carcinoma
#19
Huiying Xue, Zhaoyang Yu, Yong Liu, Weigang Yuan, Tan Yang, Jia You, Xingxing He, Robert J Lee, Lei Li, Chuanrui Xu
Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28768434/metabolic-reprogramming-during-hepatitis-b-disease-progression-offers-novel-diagnostic-and-therapeutic-opportunities
#20
REVIEW
Jesse Jr Masson, Hugh Ww Billings, Clovis S Palmer
Metabolic remodeling occurs in immune cells during an infection. Host cells must upregulate energy production for growth, proliferation, and effector functions to limit the damage imposed by pathogens. One example, the hepatitis B virus, induces hepatic injury in human hepatocytes through dysregulation of aerobic glycolysis and lipid metabolism. Increased glycolytic metabolism mediated by elevated expression of Glut1, glucose influx, and lactate secretion is associated with this Warburg phenotype, a classic metabolic signature also observed in cancer cells...
August 2017: Antiviral Chemistry & Chemotherapy
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