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hcc pathophysiology

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https://www.readbyqxmd.com/read/28063004/tubulin-alpha-8-is-expressed-in-hepatic-stellate-cells-and-is-induced-in-transformed-hepatocytes
#1
Lisa Rein-Fischboeck, Rebekka Pohl, Elisabeth M Haberl, Sebastian Zimny, Maximilian Neumann, Kristina Eisinger, Thomas S Weiss, Sabrina Krautbauer, Christa Buechler
Tubulin alpha 8 (TUBA8) is highly abundant in murine liver tumors suggesting a role in hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is a risk factor for HCC. In mice that are fed with a methionine-choline deficient diet for two weeks to induce advanced murine NASH, we do see increased hepatic levels of TUBA8 protein. In animals given a high-fat diet for 14 weeks or an atherogenic diet for 12 weeks, hepatic TUBA8 is unchanged. TUBA8 is highly expressed in human hepatic stellate cells (HSC) and co-localizes with the HSC marker desmin in the murine liver...
January 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28049764/the-scf%C3%AE-trcp-e3-ubiquitin-ligase-complex-targets-lipin1-for-ubiquitination-and-degradation-to-promote-hepatic-lipogenesis
#2
Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seira Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M Asara, Satoshi Fukumoto, Keiichi I Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, Wenyi Wei
The SCF(β-TRCP) E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF(β-TRCP) biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/27981611/grb14-inhibition-triggers-insulin-induced-mouse-hepatocyte-proliferation-and-is-associated-with-hepatocellular-carcinoma
#3
Lucille Morzyglod, Michèle Caüzac, Lucie Popineau, Pierre-Damien Denechaud, Luis Fajas, Bruno Ragazzon, Véronique Fauveau, Julien Planchais, Mireille Vasseur-Cognet, Laetitia Fartoux, Olivier Scatton, Olivier Rosmorduc, Sandra Guilmeau, Catherine Postic, Chantal Desdouets, Christèle Desbois-Mouthon, Anne-Françoise Burnol
: Metabolic diseases such as obesity and type 2 diabetes are recognized as independent risk factors for hepatocellular carcinoma (HCC). Hyperinsulinemia, a hallmark of these pathologies, is suspected to be involved in HCC development. The molecular adapter Grb14 is an inhibitor of insulin receptor (IR) catalytic activity, highly expressed in the liver. To study its involvement in hepatocyte proliferation we specifically inhibited its liver expression using an shRNA strategy in mice. Enhanced insulin signaling upon Grb14 downregulation (Grb14i) was accompanied by a transient induction of S phase entrance by quiescent hepatocytes, indicating that Grb14 is a potent repressor of cell division...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27916167/post-resection-recurrence-of-hepatocellular-carcinoma-in-cirrhotic-patients-is-thrombocytopenia-a-risk-factor-for-recurrence
#4
Ahmed Shehta, Ho-Seong Han, Soyeon Ahn, Yoo-Seok Yoon, Jai Young Cho, Young Rok Choi
PURPOSE: Liver resection is the main treatment for hepatocellular carcinoma (HCC) patients with sufficient liver reserve. However, the long-term outcomes are dismal because the recurrence rate is high, especially in cirrhotic patients. The role of platelets as a predictive factor for HCC recurrence is still controversial. The aim of this study was to assess the influence of the preoperative platelet count on HCC recurrence after liver resection in patients with liver cirrhosis. STUDY DESIGN: Between 2004 and 2013, 233 HCC patients with pathologically proven liver cirrhosis underwent liver resection and were enrolled in this study...
December 2016: Surgical Oncology
https://www.readbyqxmd.com/read/27913395/metabolomic-characterization-of-hepatocellular-carcinoma-in-patients-with-liver-cirrhosis-for-biomarker-discovery
#5
Cristina Di Poto, Alessia Ferrarini, Yi Zhao, Rency S Varghese, Chao Tu, Yiming Zuo, Minkun Wang, Mohammad R Nezami Ranjbar, Yue Luo, Chi Zhang, Chirag S Desai, Kirti Shetty, Mahlet G Tadesse, Habtom W Ressom
BACKGROUND: Metabolomics plays an important role in providing insight into the etiology and mechanisms of hepatocellular carcinoma (HCC). This is accomplished by a comprehensive analysis of patterns involved in metabolic alterations in human specimens. This study compares the levels of plasma metabolites in HCC cases versus cirrhotic patients and evaluates the ability of candidate metabolites in distinguishing the two groups. Also, it investigates the combined use of metabolites and clinical covariates for detection of HCC in patients with liver cirrhosis...
December 2, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27903585/autophagy-in-chronic-liver-diseases-the-two-faces-of-janus
#6
Philippe Gual, Helene Gilgenkrantz, Sophie Lotersztajn
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis, steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (Macroautophagy and Chaperome-mediated autophagy) and chronic liver diseases have been reported...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27899914/how-useful-are-monogenic-rodent-models-for-the-study-of-human-non-alcoholic-fatty-liver-disease
#7
REVIEW
Jake P Mann, Robert K Semple, Matthew J Armstrong
Improving understanding of the genetic basis of human non-alcoholic fatty liver disease (NAFLD) has the potential to facilitate risk stratification of affected patients, permit personalized treatment, and inform development of new therapeutic strategies. Animal models have been widely used to interrogate the pathophysiology of, and genetic predisposition to, NAFLD. Nevertheless, considerable interspecies differences in intermediary metabolism potentially limit the extent to which results can be extrapolated to humans...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27891128/immune-imbalances-in-non-alcoholic-fatty-liver-disease-from-general-biomarkers-and-neutrophils-to-interleukin-17-axis-activation-and-new-therapeutic-targets
#8
REVIEW
Feliciano Chanana Paquissi
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27890867/obesity-related-digestive-diseases-and-their-pathophysiology
#9
REVIEW
Su Youn Nam
Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer...
November 29, 2016: Gut and Liver
https://www.readbyqxmd.com/read/27889186/circadian-homeostasis-of-liver-metabolism-suppresses-hepatocarcinogenesis
#10
Nicole M Kettner, Horatio Voicu, Milton J Finegold, Cristian Coarfa, Arun Sreekumar, Nagireddy Putluri, Chinenye A Katchy, Choogon Lee, David D Moore, Loning Fu
Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27878289/oncogenic-function-of-plac1-on-the-proliferation-and-metastasis-in-hepatocellular-carcinoma-cells
#11
Yuan Wu, Xiaocong Lin, Xiaoqing Di, Yonghua Chen, Hanning Zhao, Xin Wang
Placenta-specific protein 1 (Plac1), which is selectively expressed in the placental syncytiotrophoblast in adult normal tissues, plays an essential role in normal placental and embryonic development. Accumulating evidence suggests that enhanced Plac1 expression is closely associated with the progression of human cancer. Whether Plac1 contributes to the pathophysiology of hepatocellular carcinoma (HCC) remains unclear. In the present study, our data revealed that the expression of Plac1 in human HCC tissues was upregulated, which significantly correlated with metastasis of HCC...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/27807065/clinical-and-therapeutic-implications-of-follistatin-in-solid-tumours
#12
REVIEW
Lei Shi, Jeyna Resaul, Sioned Owen, Lin Ye, Wen G Jiang
Follistatin (FST), as a single-chain glycosylated protein, has two major isoforms, FST288 and FST315. The FST315 isoform is the predominant form whilst the FST288 variant accounts for less than 5% of the encoded mRNA. FST is differentially expressed in human tissues and aberrant expression has been observed in a variety of solid tumours, including gonadal, gastric and lung cancer, hepatocellular carcinoma, basal cell carcinoma and melanoma. Based on the current evidence, FST is an antagonist of transforming growth factor beta family members, such as activin and bone morphogenetic proteins (BMPs)...
November 2016: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/27757953/animal-models-of-non-alcoholic-fatty-liver-disease-current-perspectives-and-recent-advances
#13
REVIEW
Jennie Ka Ching Lau, Xiang Zhang, Jun Yu
Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis and, in more severe cases, to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Because of its growing worldwide prevalence, various animal models that mirror both the histopathology and the pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field...
January 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27729736/hepatocellular-carcinoma-in-patients-with-non-alcoholic-fatty-liver-disease
#14
REVIEW
Carrie R Wong, Mindie H Nguyen, Joseph K Lim
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma (HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3...
October 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27721918/implication-of-the-intestinal-microbiome-in-complications-of-cirrhosis
#15
Mamatha Bhat, Bianca M Arendt, Venkat Bhat, Eberhard L Renner, Atul Humar, Johane P Allard
The intestinal microbiome (IM) is altered in patients with cirrhosis, and emerging literature suggests that this impacts on the development of complications. The PubMed database was searched from January 2000 to May 2015 for studies and review articles on the composition, pathophysiologic effects and therapeutic modulation of the IM in cirrhosis. The following combination of relevant text words and MeSH terms were used, namely intestinal microbiome, microbiota, or dysbiosis, and cirrhosis, encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular carcinoma...
September 28, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27714883/characteristics-of-c-terminal-%C3%AE-amyloid-peptide-binding-fragment-of-neuroprotective-protease-inhibitor-cystatin-c
#16
Marta Spodzieja, Katarzyna Kalejta, Aleksandra S Kołodziejczyk, Martyna Maszota-Zieleniak, Sylwia Rodziewicz-Motowidło, Wioletta Żmudzińska, Paulina Czaplewska
Cystatin C originally identified as a cysteine proteases inhibitor has a broad spectrum of biological roles ranging from inhibition of extracellular cysteine protease activities, bone resorption, and modulation of inflammatory responses to stimulation of fibroblasts proliferation. There is an increasing number of evidence to suggest that human cystatin C (hCC) might play a protective role in the pathophysiology of sporadic Alzheimer's disease. In vivo and in vitro results well documented the association of hCC with Aβ and the hCC-induced inhibition of Aβ fibril formation...
October 7, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27697092/mir-935-promotes-liver-cancer-cell-proliferation-and-migration-by-targeting-sox7
#17
Xiaorui Liu, Jingjing Li, Zujiang Yu, Juan Li, Ranran Sun, Quancheng Kan
Hepatocellular carcinoma (HCC) is the most common cancer in the world. MicroRNAs (miRNAs) are a type of small noncoding RNA that can regulate the expression of target genes under physiological and pathophysiological conditions. Aberrant expression of MicroRNA-935 (MiR-935) has been reported in cancer studies. However, its expression and mechanism in hepatocellular carcinoma remain unclear. In our study, we found that miR-935 was upregulated in liver cancer tissues and cells. Overexpression of miR-935 in liver cells promoted cell proliferation, tumorigenesis, and cell cycle progression, whereas inhibition of miR-935 reduced cell proliferation, tumorigenicity, and cell cycle progression...
September 30, 2016: Oncology Research
https://www.readbyqxmd.com/read/27690306/liver-steatosis-and-nonalcoholic-steatohepatitis-from-pathogenesis-to-therapy
#18
Elizabeth Hernández-Pérez, Plácido Enrique León García, Norma Edith López-Díazguerrero, Fernando Rivera-Cabrera, Elizabeth Del Ángel Benítez
Non-alcoholic fatty liver disease refers to a disease spectrum that ranges from steatosis to non-alcoholic steatohepatitis, which leads to fibrosis, cirrhosis and hepatocellular carcinoma. Given the increasing prevalence of obesity worldwide, the incidence of non-alcoholic fatty liver disease has become a world health problem. Non-alcoholic fatty liver disease is considered to be the hepatic manifestation of metabolic syndrome associated with insulin resistance, central obesity, and type 2 diabetes mellitus...
September 13, 2016: Medwave
https://www.readbyqxmd.com/read/27677954/hepatitis-b-virus-hbv-infection-and-hepatocellular-carcinoma-new-insights-for-an-old-topic
#19
Shi-Yan Yan, Jian-Gao Fan, Liang Qiao
Liver cancer is a common disease and the third leading cause of cancer-related deaths worldwide [1]. Hepatocellular carcinoma (HCC) is the most deadly form of liver cancer. Chronic hepatitis and subsequent liver fibrosis and cirrhosis are the major causes of HCC [2]. Chronic hepatitis B (CHB) is one of the most common infections worldwide. It is estimated that two billion people have been infected with hepatitis B virus (HBV), and up to 400,000 people worldwide are believed to have chronic HBV infection [3]...
September 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27669220/a-novel-tetraenoic-fatty-acid-isolated-from-amaranthus-spinosus-inhibits-proliferation-and-induces-apoptosis-of-human-liver-cancer-cells
#20
Arijit Mondal, Tanmoy Guria, Tapan Kumar Maity, Anupam Bishayee
Amaranthus spinosus Linn. (Family: Amaranthaceae) has been shown to be useful in preventing and mitigating adverse pathophysiological conditions and complex diseases. However, only limited information is available on the anticancer potential of this plant. In this study, we examined the antiproliferative and pro-apoptotic effects of a novel fatty acid isolated from A. spinosus-(14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate-against HepG2 human liver cancer cells. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine cell viability, flow cytometry assay for cell cycle analysis, and Western blot analysis to measure protein expression of Cdc2), cyclin B1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2)...
September 22, 2016: International Journal of Molecular Sciences
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