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https://www.readbyqxmd.com/read/29131160/human-primary-liver-cancer-derived-organoid-cultures-for-disease-modeling-and-drug-screening
#1
Laura Broutier, Gianmarco Mastrogiovanni, Monique Ma Verstegen, Hayley E Francies, Lena Morrill Gavarró, Charles R Bradshaw, George E Allen, Robert Arnes-Benito, Olga Sidorova, Marcia P Gaspersz, Nikitas Georgakopoulos, Bon-Kyoung Koo, Sabine Dietmann, Susan E Davies, Raaj K Praseedom, Ruby Lieshout, Jan N M IJzermans, Stephen J Wigmore, Kourosh Saeb-Parsy, Mathew J Garnett, Luc Jw van der Laan, Meritxell Huch
Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors...
November 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29074727/liver-reptin-ruvbl2-controls-glucose-and-lipid-metabolism-with-opposite-actions-on-mtorc1-and-mtorc2-signalling
#2
Joaquim Javary, Nathalie Allain-Courtois, Nicolas Saucisse, Pierre Costet, Capucine Heraud, Fadila Benhamed, Rémi Pierre, Corinne Bure, Nestor Pallares-Lupon, Marcio Do Cruzeiro, Catherine Postic, Daniela Cota, Pierre Dubus, Jean Rosenbaum, Samira Benhamouche-Trouillet
OBJECTIVE: The AAA+ ATPase Reptin is overexpressed in hepatocellular carcinoma and preclinical studies indicate that it could be a relevant therapeutic target. However, its physiological and pathophysiological roles in vivo remain unknown. This study aimed to determine the role of Reptin in mammalian adult liver. DESIGN AND RESULTS: We generated an inducible liver-specific Reptin knockout (Repin(LKO) ) mouse model. Following Reptin invalidation, mice displayed decreased body and fat mass, hypoglycaemia and hypolipidaemia...
October 26, 2017: Gut
https://www.readbyqxmd.com/read/29068390/does-hypoxia-cause-carcinogenic-iron-accumulation-in-alcoholic-liver-disease-ald
#3
REVIEW
Inês Silva, Vanessa Rausch, Helmut-Karl Seitz, Sebastian Mueller
Alcoholic liver disease (ALD) is a leading health risk worldwide. Hepatic iron overload is frequently observed in ALD patients and it is an important and independent factor for disease progression, survival, and the development of primary liver cancer (HCC). At a systemic level, iron homeostasis is controlled by the liver-secreted hormone hepcidin. Hepcidin regulation is complex and still not completely understood. It is modulated by many pathophysiological conditions associated with ALD, such as inflammation, anemia, oxidative stress/H₂O2, or hypoxia...
October 25, 2017: Cancers
https://www.readbyqxmd.com/read/29058484/neurite-outgrowth-inhibitor-b-receptor-a-versatile-receptor-with-multiple-functions-and-actions
#4
Shuang-Lian Long, Yu-Kun Li, Yuan-Jie Xie, Zhi-Feng Long, Jin-Feng Shi, Zhong-Cheng Mo
Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis...
October 23, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29040986/comparison-of-sofosbuvir-plus-ribavirin-treatment-with-pegylated-interferon-plus-ribavirin-treatment-for-chronic-hepatitis-c-genotype-2
#5
Kayo Seo, Soo Ki Kim, Soo Ryang Kim, Aya Ohtani, Mana Kobayashi, Airi Kato, Eri Morimoto, Yuka Saijo, Ke Ih Kim, Susumu Imoto, Chi Wan Kim, Yoshihiko Yano, Masatoshi Kudo, Yoshitake Hayashi
BACKGROUND: Sofosbuvir plus ribavirin (RBV) therapy showed higher sustained virological response at 12 weeks after treatment (SVR12) than pegylated interferon (peg-IFN) plus RBV; however, liver function, fibrosis, and hepatocellular carcinoma markers have not been assessed so far. SUMMARY: Patients (n = 21) receiving Sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus RBV were enrolled in this study. Changes in alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels, platelet (PLT) counts, FIB-4, and aspartate aminotransferase-to-platelet ratio index (APRI) in both groups were assessed in patients achieving SVR12...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28976505/pandar-a-pivotal-cancer-related-long-non-coding-rna-in-human-cancers
#6
REVIEW
Jinglin Li, Zhenglong Li, Wangyang Zheng, Xinheng Li, Zhidong Wang, Yunfu Cui, Xingming Jiang
Long non-coding RNAs (lncRNAs), non-protein-coding RNAs that are more than 200 nucleotides in length, have been demonstrated to play a vital role in the pathophysiology of human diseases, particularly in tumorigenesis and progression of cancers. Dysregulation of lncRNAs, which serve as either oncogenes or tumor suppressor genes, is involved in diverse cellular processes, such as proliferation, dedifferentiation, migration, invasion and anti-apoptosis. Promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR), which was recently found to manifest aberrant expression in various malignancies including non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer and gastric cancer, is a novel cancer-related lncRNA...
October 24, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28933169/-history-and-presence-of-hepatitis-b%C3%A2-and-c%C3%A2-therapy
#7
Petr Husa
Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the worlds major causes of chronic liver disease. Care of patients infected with HBV and HCV and/or over the last 20 years has significantly improved thanks to the better understanding of the pathophysiology of disease, improvement of diagnostic, therapeutic and preventive options. The goal of treatment of chronic hepatitis B is to extend the length of life and improve its quality through the barriers of the progression of chronic hepatitis to cirrhosis, decompensation cirrhosis and hepatocellular carcinoma (HCC)...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28914862/-liver-diseases-the-pathogenetic-role-of-the-gut-microbiome-and-the-potential-of-treatment-for-its-modulation
#8
K A Aitbaev, I T Murkamilov, V V Fomin
The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28903501/sex-differential-responses-of-tumor-promotion-associated-genes-and-dysregulation-of-novel-long-noncoding-rnas-in-constitutive-androstane-receptor-activated-mouse-liver
#9
Nicholas J Lodato, Tisha Melia, Andy Rampersaud, David J Waxman
Xenobiotic agonists of constitutive androstane receptor (CAR) induce many hepatic drug metabolizing enzymes, but following prolonged exposure, promote hepatocellular carcinoma, most notably in male mouse liver. Here, we used nuclear RNA-seq to characterize global changes in the mouse liver transcriptome following exposure to the CAR-specific agonist ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), including changes in novel long noncoding RNAs that may contribute to xenobiotic-induced pathophysiology...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28893365/coffee-consumption-and-prevention-of-cirrhosis-in-support-of-the-caffeine-hypothesis
#10
Jonathan Dranoff
It is widely acknowledged that coffee is the most widely used drug on Earth. While this is true, coffee is also a foodstuff with wide variation, so its use is often directed at satisfying dietary urges. When used as a drug, coffee is almost invariably used as a stimulant rather than to treat or prevent particular diseases. Thus, it has been an exciting revelation in recent years that coffee consumption is inversely related to progression of liver fibrosis to cirrhosis and even hepatocellular carcinoma.As is often the case, epidemiological observations have preceded pathophysiological explanations for this effect...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28884871/lncrna-atb-an-indispensable-cancer-related-long-noncoding-rna
#11
REVIEW
Jinglin Li, Zhenglong Li, Wangyang Zheng, Xinheng Li, Zhidong Wang, Yunfu Cui, Xingming Jiang
OBJECTIVES: Long non-coding RNAs (lncRNAs) are a group of non-protein-coding RNAs that are greater than 200 nucleotides in length. Increasing evidence indicates that lncRNAs, which may serve as either oncogenes or tumour suppressor genes, play a vital role in the pathophysiology of human diseases, especially in tumourigenesis and progression. Deregulation of lncRNAs impacts different cellular processes, such as proliferation, dedifferentiation, migration, invasion and anti-apoptosis. The aim of this review was to explore the molecular mechanism and clinical significance of long non-coding RNA-activated by transforming growth factor β (lncRNA-ATB) in various types of cancers...
September 8, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28858692/modeling-hepatitis-virus-infections-and-treatment-strategies-in-humanized-mice
#12
REVIEW
Dina Kremsdorf, Helene Strick-Marchand
Hepatitis viruses cause chronic liver diseases such as fibrosis, cirrhosis and hepatocellular carcinomas that are difficult to treat and constitute a global health problem. Species-specific viral tropism has limited the usefulness of small animal models to study the impact of viral hepatitis. Immunodeficient mice grafted with human hepatocytes are susceptible to hepatitis viruses B, C, D and E (HBV, HCV, HDV and HEV), developing full viral life cycles, and delivering a means to investigate virus-host interactions and antiviral treatments...
August 28, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28836282/white-matter-fiber-integrity-of-the-saccadic-eye-movement-network-differs-between-schizophrenia-and-healthy-groups
#13
David J Schaeffer, Amanda L Rodrigue, Courtney R Burton, Jordan E Pierce, Megan N Murphy, Brett A Clementz, Jennifer E McDowell
Recent diffusion tensor imaging (DTI) studies suggest that altered white matter fiber integrity is a pathophysiological feature of schizophrenia. Lower white matter integrity is associated with poor cognitive control, a characteristic of schizophrenia that can be measured using antisaccade tasks. Although the functional neural correlates of poor antisaccade performance have been well documented, fewer studies have investigated the extent to which white matter fibers connecting the functional nodes of this network contribute to antisaccade performance...
August 23, 2017: Psychophysiology
https://www.readbyqxmd.com/read/28800792/microrna-125a-5p-inhibits-cell-proliferation-and-induces-apoptosis-in-hepatitis-b-virus-related-hepatocellular-carcinoma-by-downregulation-of-erbb3
#14
Guoyun Li, Wei Zhang, Li Gong, Xiaoping Huang
MicroRNAs, a class of endogenous non-coding RNAs, regulate gene expression at post-transcriptional level, thus taking part in multiple biological processed. Increasing miRNAs are found to be dysregulated in hepatocellular carcinoma (HCC) and are involved in liver tumorigenesis. In this study, miR-125a-5p was found to obviously downregulate much more in hepatitis B virus (HBV)-related HCC. To investigate the effects of miR-125a-5p, miR-125a-5p was overexpressed in HepG2.2.15 and HepG3X cells, respectively. The findings have indicated that overexpression of miR-125a-5p dramatically inhibited cell proliferation and induced cell apoptosis...
August 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28781795/transmembrane-channel-like-protein-8-as-a-potential-biomarker-for-poor-prognosis-of-hepatocellular-carcinoma
#15
Panpan Lu, Qiang Ding, Shuping Ding, Yuhui Fan, Xin Li, Dean Tian, Mei Liu
Hepatocellular carcinoma (HCC) is an aggressive malignant tumor and the third leading cause of cancer-related mortality worldwide. Transmembrane channel-like protein 8 (TMC8) is reported to play a major role in several aspects of human pathophysiology, such as ion channel permeability, human papillomavirus infection and skin cancer; however, its role in HCC has not been fully elucidated. The aim of the present study was to investigate the expression levels of TMC8 in 146 pairs of liver cancer samples and adjacent non-tumorous samples using immunohistochemistry...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28752441/pathophysiology-of-alpha-1-antitrypsin-deficiency-liver-disease
#16
Jeffrey H Teckman, Keith S Blomenkamp
Classical alpha-1 antitrypsin (a1AT) deficiency is an autosomal recessive disease associated with an increased risk of liver disease in adults and children, and with lung disease in adults (Teckman and Jain, Curr Gastroenterol Rep 16(1):367, 2014). The vast majority of the liver disease is associated with homozygosity for the Z mutant allele, the so-called PIZZ. These homozygous individuals synthesize large quantities of a1AT mutant Z protein in the liver, but the mutant protein folds improperly during biogenesis and approximately 85% of the molecules are retained within the hepatocytes rather than appropriately secreted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730823/pathophysiological-analysis-of-the-progression-of-hepatic-lesions-in-stam-mice
#17
T Saito, M Muramatsu, Y Ishii, Y Saigo, T Konuma, Y Toriniwa, K Miyajima, T Ohta
Nonalcoholic steatohepatitis (NASH) is a current health issue since the disease often leads to hepatocellular carcinoma; however, the pathogenesis of the disease has still not been fully elucidated. In this study, we investigated the pathophysiological changes observed in hepatic lesions in STAM mice, a novel NASH model. STAM mice, high fat-diet (HFD) fed mice, and streptozotocin (STZ) treated mice were prepared, and changes over time, such as biological parameters, mRNA expression, and histopathological findings, were evaluated once animal reached 5, 7, and 10 weeks of age...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28702738/impact-of-etiological-treatment-on-prognosis
#18
REVIEW
Chien-Wei Su, Ying-Ying Yang, Han-Chieh Lin
Portal hypertension (PHT) is a frequent and severe complication of cirrhosis. PHT may lead to the development of various complications with high mortality. Liver transplantation is the gold standard as a surgical curative treatment for end-stage liver disease. Theoretically, etiological treatment focusing on the pathophysiology of the underlying disease should be the objective of the nonsurgical management of cirrhotic PHT. Chronic viral hepatitis is the major etiology of cirrhosis and PHT. In cirrhotic patients with chronic hepatitis B virus infection, antiviral therapies can suppress viral replication, ameliorate hepatic inflammation, regress fibrosis, and restore liver functional reserve...
July 12, 2017: Hepatology International
https://www.readbyqxmd.com/read/28685993/association-of-single-nucleotide-polymorphisms-in-micrornas-with-susceptibility-to-hepatitis-b-virus-infection-and-hbv-related-liver-complications-a-study-in-a-saudi-arabian-population
#19
Ahmed A Al-Qahtani, Mashael R Al-Anazi, Nyla Nazir, Kaiser Wani, Ayman A Abdo, Faisal M Sanai, Mohammed Q Khan, Hamad I Al-Ashgar, Ali Albenmousa, Waleed K Al-Hamoudi, Khalid A Alswat, Mohammed N Al-Ahdal
The aim of this study was to evaluate the association of 10 SNPs in different microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV clearance, persistence of chronic HBV infection, and progression to liver cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the following groups: inactive HBV carrier, active HBV carrier, HBV-cleared subject, and cirrhosis+HCC. Samples were analyzed for 10 SNPs in microRNAs using either PCR-based genotyping or the TaqMan assay...
July 7, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28652891/non-alcoholic-fatty-liver-disease-an-expanded-review
#20
REVIEW
Mark Benedict, Xuchen Zhang
Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology...
June 8, 2017: World Journal of Hepatology
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