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https://www.readbyqxmd.com/read/28532995/histological-subtypes-of-hepatocellular-carcinoma-are-related-to-gene-mutations-and-molecular-tumour-classification
#1
Julien Calderaro, Gabrielle Couchy, Sandrine Imbeaud, Giuliana Amaddeo, Eric Letouzé, Jean-Frédéric Blanc, Christophe Laurent, Yacine Hajji, Daniel Azoulay, Paulette Bioulac-Sage, Jean-Charles Nault, Jessica Zucman-Rossi
BACKGROUND AND AIMS: Our increasing understanding of hepatocellular carcinoma (HCC) biology holds promise for personalized care, however its translation into clinical practice requires a precise knowledge of its relationship to tumour phenotype. METHODS: We aimed at investigating molecular-phenotypic correlations in a large series of HCC. To this purpose, 343 surgically resected HCC were investigated by pathological review, immunohistochemistry, gene expression profiling and sequencing...
May 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28511023/efficacy-of-docosahexaenoic-acid-choline-vitamin-e-dha-cho-ve-in-paediatric-nash-a-randomized-controlled-clinical-trial
#2
Evelyn Zöhrer, Alisi Anna, Jörg Jahnel, Antonella Moscla, Claudia Della Corte, Annalisa Crudele, Günter Fauler, Valerio Nobili
Non-alcoholic steatohepatitis (NASH), a progressive form of non-alcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children. We conducted a randomized controlled clinical trial on children with biopsy-proven NASH based on a combinatorial nutritional approach compared to placebo. Participants were assigned to lifestyle modification plus placebo, or lifestyle modification plus a mix containing docosahexaenoic acid, choline and vitamin E (DHA-CHO-VE). Forty children and adolescents concluded the trial...
May 16, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28508871/non-cell-autonomous-activation-of-il-6-stat3-signaling-mediates-fgf19-driven-hepatocarcinogenesis
#3
Mei Zhou, Hong Yang, R Marc Learned, Hui Tian, Lei Ling
Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is the second leading cause of cancer mortality worldwide. Fibroblast Growth Factor 19 (FGF19) is one of the most frequently amplified genes in HCC patients. Moreover, mice expressing an FGF19 transgene have been shown to develop HCC. However, the downstream signalling pathways that mediate FGF19-dependent tumorigenesis remain to be deciphered. Here we show that FGF19 triggers a previously unsuspected, non-cell-autonomous program to activate STAT3 signalling in hepatocytes through IL-6 produced in the liver microenvironment...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507750/effects-of-conventional-and-a-novel-colonic-release-bile-acid-sequestrant-a3384-on-fibroblast-growth-factor-19-and-bile-acid-metabolism-in-healthy-volunteers-and-patients-with-bile-acid-diarrhoea
#4
R N Appleby, A Bajor, P-G Gillberg, H Graffner, M Simrén, K A Ung, Jrf Walters
BACKGROUND: Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. AIM: The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD...
April 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28498614/hepatic-uptake-of-conjugated-bile-acids-is-mediated-by-both-ntcp-and-oatps-and-modulated-by-intestinal-sensing-of-plasma-bile-acid-levels-in-mice
#5
Davor Slijepcevic, Reinout L P Roscam Abbing, Takeshi Katafuchi, Antje Blank, Joanne M Donkers, Stéphanie van Hoppe, Dirk R de Waart, Dagmar Tolenaars, Jonathan H M van der Meer, Manon Wildenberg, Ulrich Beuers, Ronald P J Oude Elferink, Alfred H Schinkel, Stan F J van de Graaf
BACKGROUND & AIMS: The Na(+) -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. METHODS: Mice or healthy volunteers were treated with myrcludex B...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28487440/cholestyramine-treatment-of-healthy-humans-rapidly-induces-transient-hypertriglyceridemia-when-treatment-is-initiated
#6
Beatrice Sjöberg, Sara Straniero, Bo Angelin, Mats Rudling
Bile acid (BA) production in mice is regulated by hepatic farnesoid X receptors and by intestinal fibroblast growth factor (FGF) 15, (in humans FGF19) a suppressor of BA synthesis that also reduces serum triglycerides and glucose. Cholestyramine treatment reduces FGF19 and induces BA synthesis while plasma triglycerides may increase of unclear reasons. We explored if FGF19 may suppress BA synthesis and plasma triglycerides in humans by modulation of FGF19 levels through long-term cholestyramine at increasing doses...
May 9, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28460066/co-clinical-trials-demonstrate-predictive-biomarkers-for-dovitinib-an-fgfr-inhibitor-in-lung-squamous-cell-carcinoma
#7
H R Kim, H N Kang, H S Shim, E Y Kim, J Kim, D J Kim, J G Lee, C Y Lee, M H Hong, S-M Kim, H Kim, K-H Pyo, M R Yun, H J Park, J Y Han, H A Youn, M-J Ahn, S Paik, T-M Kim, B C Cho
Background: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). Methods: : The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling...
April 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28451950/the-role-and-potential-therapeutic-implications-of-the-fibroblast-growth-factors-in-energy-balance-and-type-2-diabetes
#8
REVIEW
Maitane Izaguirre, María J Gil, Ignacio Monreal, Fabrizio Montecucco, Gema Frühbeck, Victoria Catalán
PURPOSE OF REVIEW: Obesity and its associated metabolic diseases have reached epidemic proportions worldwide, reducing life expectancy and quality of life. Several drugs have been tested to treat these diseases but many of them have damaging side effects. Consequently, there is an urgent need to develop more effective therapies. Recently, endocrine fibroblast growth factors (FGFs) have become attractive targets in the treatment of metabolic diseases. This review summarizes their most important functions as well as FGF-based therapies for the treatment of obesity and type 2 diabetes (T2D)...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28446510/a-postprandial-fgf19-shp-lsd1-regulatory-axis%C3%A2-mediates-epigenetic-repression-of-hepatic%C3%A2-autophagy
#9
Sangwon Byun, Young-Chae Kim, Yang Zhang, Bo Kong, Grace Guo, Junichi Sadoshima, Jian Ma, Byron Kemper, Jongsook Kim Kemper
Lysosome-mediated autophagy is essential for cellular survival and homeostasis upon nutrient deprivation, but is repressed after feeding. Despite the emerging importance of transcriptional regulation of autophagy by nutrient-sensing factors, the role for epigenetic control is largely unexplored. Here, we show that Small Heterodimer Partner (SHP) mediates postprandial epigenetic repression of hepatic autophagy by recruiting histone demethylase LSD1 in response to a late fed-state hormone, FGF19 (hFGF19, mFGF15)...
April 26, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#10
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413172/the-effects-of-metformin-on-fibroblast-growth-factor-19-21-and-fibroblast-growth-factor-receptor-1-in-high-fat-diet-and-streptozotocin-induced-diabetic-rats
#11
Yan Wang, Ningning Dang, Pei Sun, Jin Xia, Chunxue Zhang, Shuguang Pang
To understand metformin’s effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was detected to explain the possible mechanisms. T2DM was induced by feeding rats with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ, 30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow; diabetic rats (DM) were fed on high-fat diet supplemented with or without metformin (METF) for 12 weeks (500 mg・kg(-1)・d(-1))...
April 11, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28378364/chenodeoxycholic-acid-stimulated-fibroblast-growth-factor-19-response-a-potential-biochemical-test-for-bile-acid-diarrhoea
#12
C Borup, S Wildt, J J Rumessen, P N Bouchelouche, J Graff, M Damgaard, C McQuitty, D Rainteau, L K Munck
BACKGROUND: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. AIM: To explore if an impaired FGF19 response identifies primary bile acid diarrhoea. METHODS: Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal...
June 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28274997/what-if-prometheus-had-steatosis-potential-use-of-fgf19-to-promote-regeneration-of-the-fatty-liver
#13
Philip M Brown, Yaron Rotman
No abstract text is available yet for this article.
March 8, 2017: Gut
https://www.readbyqxmd.com/read/28261926/acute-caloric-restriction-counteracts-hepatic-bile-acid-and-cholesterol-deficiency-in-morbid-obesity
#14
S Straniero, F Rosqvist, D Edholm, H Ahlström, J Kullberg, M Sundbom, U Risérus, M Rudling
BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver...
May 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28249259/fibroblast-growth-factor-15-19-in-hepatocarcinogenesis
#15
REVIEW
Gloria Alvarez-Sola, Iker Uriarte, M Ujue Latasa, Raquel Urtasun, Marina Bárcena-Varela, Maria Elizalde, Maddalen Jiménez, Carlos M Rodriguez-Ortigosa, Fernando J Corrales, Maite G Fernández-Barrena, Carmen Berasain, Matías A Avila
BACKGROUND: Advanced hepatocellular carcinoma (HCC) is a neoplastic disease with a very bad prognosis and increasing worldwide incidence. HCCs are resistant to conventional chemotherapy and the multikinase inhibitor sorafenib is the only agent that has shown some clinical efficacy. It is therefore important to identify key molecular mechanisms driving hepatocarcinogenesis for the development of more efficacious therapies. However, HCCs are heterogeneous tumors and different molecular subclasses have been characterized...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28178326/quantitative-liver-proteomics-identifies-fgf19-targets-that-couple-metabolism-and-proliferation
#16
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Boudewijn M T Burgering, Saskia W C van Mil
Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28119353/fibroblast-growth-factor-15-19-fgf15-19-protects-from-diet-induced-hepatic-steatosis-development-of-an-fgf19-based-chimeric-molecule-to-promote-fatty-liver-regeneration
#17
Gloria Alvarez-Sola, Iker Uriarte, M Ujue Latasa, Maite G Fernandez-Barrena, Raquel Urtasun, Maria Elizalde, Marina Barcena-Varela, Maddalen Jiménez, Haisul C Chang, Roberto Barbero, Victoria Catalán, Amaia Rodríguez, Gema Frühbeck, José M Gallego-Escuredo, Aleix Gavaldà-Navarro, Francesc Villarroya, Carlos M Rodriguez-Ortigosa, Fernando J Corrales, Jesus Prieto, Pedro Berraondo, Carmen Berasain, Matias A Avila
OBJECTIVE: Fibroblast growth factor 15/19 (FGF15/19), an enterokine that regulates synthesis of hepatic bile acids (BA), has been proposed to influence fat metabolism. Without FGF15/19, mouse liver regeneration after partial hepatectomy (PH) is severely impaired. We studied the role of FGF15/19 in response to a high fat diet (HFD) and its regulation by saturated fatty acids. We developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration...
January 24, 2017: Gut
https://www.readbyqxmd.com/read/28091894/mechanisms-of-action-of-surgical-interventions-on-weight-related-diseases-the-potential-role-of-bile-acids
#18
REVIEW
Mohsen Mazidi, Pedro Paulo P de Caravatto, John R Speakman, Ricardo V Cohen
Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear...
March 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28069043/fgf19-fgfr4-signaling-contributes-to-the-resistance-of-hepatocellular-carcinoma-to-sorafenib
#19
Lixia Gao, Xuli Wang, Yaoliang Tang, Shuang Huang, Chien-An Andy Hu, Yong Teng
BACKGROUND: Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to sorafenib therapy. METHODS: FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28065787/intestinal-farnesoid-x-receptor-controls-transintestinal-cholesterol-excretion-in-mice
#20
Jan Freark de Boer, Marleen Schonewille, Marije Boesjes, Henk Wolters, Vincent W Bloks, Trijnie Bos, Theo H van Dijk, Angelika Jurdzinski, Renze Boverhof, Justina C Wolters, Jan A Kuivenhoven, Jan M van Deursen, Ronald P J Oude Elferink, Antonio Moschetta, Claus Kremoser, Henkjan J Verkade, Folkert Kuipers, Albert K Groen
BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway, however, are poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. METHODS: We performed studies with C57Bl/6J mice, as well as with mice with intestine-specific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-knockout mice...
January 5, 2017: Gastroenterology
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