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https://www.readbyqxmd.com/read/28535186/fxr-gankyrin-axis-is-involved-in-development-of-pediatric-liver-cancer
#1
Leila Valanejad, Kyle Lewis, Mary Wright, Yanjun Jiang, Amber D'Souza, Rebekah Karns, Rachel Sheridan, Anita Gupta, Kevin Bove, David Witte, James Geller, Gregory Tiao, David L Nelson, Lubov Timchenko, Nikolai Timchenko
The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28534998/proliferation%C3%A2-inhibiting-pathways-in-liver-regeneration-review
#2
Menggang Liu, Ping Chen
Liver regeneration, an orchestrated process, is the primary compensatory mechanism following liver injury caused by various factors. The process of liver regeneration consists of three stages: Initiation, proliferation and termination. Proliferation‑promoting factors, which stimulate the recovery of mitosis in quiescent hepatocytes, are essential in the initiation and proliferation steps of liver regeneration. Proliferation‑promoting factors act as the 'motor' of liver regeneration, whereas proliferation inhibitors arrest cell proliferation when the remnant liver reaches a suitable size...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28518148/hepatocyte-polyploidization-and-its-association-with-pathophysiological-processes
#3
REVIEW
Min-Jun Wang, Fei Chen, Joseph T Y Lau, Yi-Ping Hu
A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28498799/dietary-luteolin-attenuates-chronic-liver-injury-induced-by-mercuric-chloride-via-the-nrf2-nf-%C3%AE%C2%BAb-p53-signaling-pathway-in-rats
#4
Haili Zhang, Xiao Tan, Daqian Yang, Jingjing Lu, Biying Liu, Ruiqi Baiyun, Zhigang Zhang
Mercury exposure is a common cause of metal poisoning which is biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. Luteolin, a phenolic compound found in many natural products, has multiple biological functions. Our study was aimed to explore the biological effects of luteolin in a liver injury model induced in rats by mercuric chloride (HgCl2). Criteria for injury included liver enzyme, glutathione and malondialdehyde levels, histopathology, TUNEL assay, hepatocyte viability and reactive oxygen species levels...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480888/hepatic-p63-regulates-steatosis-via-ikk%C3%AE-er-stress
#5
Begoña Porteiro, Marcos F Fondevila, Teresa C Delgado, Cristina Iglesias, Monica Imbernon, Paula Iruzubieta, Javier Crespo, Amaia Zabala-Letona, Johan Fernø, Bárbara González-Terán, Nuria Matesanz, Lourdes Hernández-Cosido, Miguel Marcos, Sulay Tovar, Anxo Vidal, Julia Sánchez-Ceinos, Maria M Malagon, Celia Pombo, Juan Zalvide, Arkaitz Carracedo, Xabier Buque, Carlos Dieguez, Guadalupe Sabio, Miguel López, Patricia Aspichueta, María L Martínez-Chantar, Ruben Nogueiras
p53 family members control several metabolic and cellular functions. The p53 ortholog p63 modulates cellular adaptations to stress and has a major role in cell maintenance and proliferation. Here we show that p63 regulates hepatic lipid metabolism. Mice with liver-specific p53 deletion develop steatosis and show increased levels of p63. Down-regulation of p63 attenuates liver steatosis in p53 knockout mice and in diet-induced obese mice, whereas the activation of p63 induces lipid accumulation. Hepatic overexpression of N-terminal transactivation domain TAp63 induces liver steatosis through IKKβ activation and the induction of ER stress, the inhibition of which rescues the liver functions...
May 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28461158/pancreatic-stellate-cells-increase-pancreatic-cancer-cells-invasion-through-the-hepatocyte-growth-factor-c-met-survivin-regulated-by-p53-p21
#6
Xiao-Peng Yang, Shang-Long Liu, Jian-Fei Xu, Shou-Gen Cao, Yu Li, Yan-Bing Zhou
Pancreatic stellate cells (PSCs) are a key cellular component of the pancreatic tumor microenvironment and are considered to contribute to tumor invasion and metastasis. Multiple cytokines and growth factors derived from PSCs are involved in malignant cancer progression, including hepatocyte growth factor (HGF). However, the molecular mechanisms by which HGF regulates cancer invasion and metastasis have not been completely elucidated. Here, we report that two pancreatic cancer (PC) cell lines, Panc-1 and SW1990, displayed different invasive and migratory abilities after treatment with HGF secreted by PSCs...
April 29, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28421122/potential-antitumor-activity-and-apoptosis-induction-of-glossostemon-bruguieri-root-extract-against-hepatocellular-carcinoma-cells
#7
Mona S Alwhibi, Mahmoud I M Khalil, Mohamed M Ibrahim, Gehan A El-Gaaly, Ahmed S Sultan
Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This study was performed to investigate the antiproliferative effects of moghat root extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC) cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked immunosorbent assay, caspase and apoptotic activation, flow cytometry, and immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 ± 6 μg/ml) and for Hep3B (1510 ± 5 μg/ml) induced significant growth-inhibitory effects against HCC cells, with no cytotoxic effect on normal hepatocytes...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28408319/deriving-and-testing-of-dysplastic-murine-hepatocytes-a-new-platform-in-liver-cancer-research
#8
Sharon Pok, Harpreet Vohra, Charbel Wehbe, Vanessa A Barn, Evi Arfianti, Yock-Young Dan, Geoffrey C Farrell, Narci C Teoh
Dysplastic hepatocytes(DH) represent altered hepatocytes with potential for malignant transformation. To date, most research on pathways to hepatocarcinogenesis has focused on use of "hepatoma" cell-lines derived from hepatocellular carcinoma(HCC). We describe a novel technique for deriving/culturing DH and demonstrate their utility for functional studies in vitro, compared to primary hepatocytes(PH) and HCC. PH and DH were prepared by portal vein collagenase perfusion from C57BL/6J mice. DH were subsequently subjected to FACS...
April 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28407767/e167k-polymorphism-of-tm6sf2-gene-affects-cell-cycle-of-hepatocellular-carcinoma-cell-hepa-1-6
#9
Shuixian Du, Linlin Lu, Yingxia Miao, Wenwen Jin, Changfei Li, Yongning Xin, Shiying Xuan
BACKGROUND: Some studties reported that the polymorphism of TM6SF2 gene E167K affects the occurrence and the progression of hepatocytes carcinoma (hepatocellular, HCC). In oeder to investigate the effects of the polymorphism of TM6SF2 gene E167K in the pathogenesis of HCC, we explored its influence on the cell cycle in hepatocellular carcinoma cell HEPA1-6. METHODS: HEPA 1-6 cells which could respectively overexpress TM6SF2 wild type and E167K variant were cultured and HEPA 1-6 cells with zero load plasmids were used as matched control...
April 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28402954/chaperone-mediated-autophagy-compensates-for-impaired-macroautophagy-in-the-cirrhotic-liver-to-promote-hepatocellular-carcinoma
#10
Srinivas Chava, Christine Lee, Yucel Aydin, Partha K Chandra, Asha Dash, Milad Chedid, Swan N Thung, Krzysztof Moroz, Tong Wu, Nabeen C Nayak, Srikanta Dash
Macroautophagy and chaperone-mediated autophagy (CMA) represent two major lysosomal degradation processes and often compensate for one another to facilitate cell survival. The aim of this study was to determine whether these autophagy pathways could compensate for one another to promote HCC cell survival in the cirrhotic liver. Analysis of normal liver tissue showed no expression of glypican-3 or p62 proteins, suggesting that macroautophagy is the major contributor to autophagic flux under non-pathological conditions...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28381798/gallic-acid-and-dodecyl-gallate-prevents-carbon-tetrachloride-induced-acute-and-chronic-hepatotoxicity-by-enhancing-hepatic-antioxidant-status-and-increasing-p53-expression
#11
Marlene Raimunda Andreola Perazzoli, Camila Katerin Perondi, Cesar Milton Baratto, Evelyn Winter, Tânia Beatriz Creczynski-Pasa, Claudriana Locatelli
Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a natural phenolic acid has been reported as a strong antioxidant. Therefore the present study was designed to evaluate the effects of GA and dodecyl gallate (DGA) against acute and chronic carbon tetrachloride (CCl4)-induced hepatotoxicity. For acute model, rats were orally treated with GA and DGA for 7 d prior to CCl4 by intraperitoneally (i.p.) injection. For the chronic model, rats were orally treated with GA or DGA and CCl4 i.p. twice a week for four weeks...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28337887/up-regulation-of-mir-888-5p-in-hepatocellular-carcinoma-cell-lines-and-its-effect-on-malignant-characteristics-of-cells
#12
E Hao, J Yu, S Xie, W Zhang, G Wang
MicroRNA (miRNA) expression has been linked to the molecular pathogenesis of hepatocellular carcinoma (HCC). The aberrant expression of miRNA is involved in the processes of tumorigenesis and cancer progression. According to the latest research, miR-888-5p is associated with strong cancer-promoting effect. For instance, miR-888-5p is up-regulated in prostate cancer and breast cancer. Nevertheless, the role of miR-888-5p in HCC has not been investigated to date. In this study, we found that miR-888-5p levels in four HCC cell lines (SMMC7721, HepG2, Huh-7 and Bel7402) were significantly up-regulated compared with human hepatocyte cell line (HHL-5)...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28321271/parkin-in-cancer-mitophagy-related-unrelated-tasks
#13
EDITORIAL
Nabil Eid, Yoichi Kondo
Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondria via a process termed mitophagy, Parkin-mediated mitophagy may be a tumor-suppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28252653/endogenous-ampk-acts-as-a-detrimental-factor-in-fulminant-hepatitis-via-potentiating-jnk-dependent-hepatocyte-apoptosis
#14
Kai Hu, Xianqiong Gong, Qing Ai, Ling Lin, Jie Dai, Lu Cai, Rong Jiang, Pu Ge, Li Zhang
The energy sensor AMP-activated protein kinase (AMPK) is crucial for energy homeostasis. Recent studies have revealed that AMPK is involved in various energy-intensive pathological processes such as inflammation and apoptosis. The physiological functions of hepatic AMPK have been well studied, but the pathological significance of AMPK in liver disorders remains largely unknown. In the present study, the phosphorylation status and the roles of AMPK were investigated in mice with lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced fulminant hepatitis...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28212554/afb1-hepatocarcinogenesis-is-via-lipid-peroxidation-that-inhibits-dna-repair-sensitizes-mutation-susceptibility-and-induces-aldehyde-dna-adducts-at-p53-mutational-hotspot-codon-249
#15
Mao-Wen Weng, Hyun-Wook Lee, Bongkun Choi, Hsiang-Tsui Wang, Yu Hu, Manju Mehta, Dhimant Desai, Shantu Amin, Yi Zheng, Moon-Shong Tang
Aflatoxin B1 (AFB1) contamination in the food chain is a major cause of hepatocellular carcinoma (HCC). More than 60% of AFB1 related HCC carry p53 codon 249 mutations but the causal mechanism remains unclear. We found that 1) AFB1 induces two types of DNA adducts in human hepatocytes, AFB1-8,9-epoxide-deoxyguanosine (AFB1-E-dG) induced by AFB1-E and cyclic α-methyl-γ-hydroxy-1,N2-propano-dG (meth-OH-PdG) induced by lipid peroxidation generated acetaldehyde (Acet) and crotonaldehyde (Cro); 2) the level of meth-OH-PdG is >30 fold higher than the level of AFB1-E-dG; 3) AFB1, Acet, and Cro, but not AFB1-E, preferentially induce DNA damage at codon 249; 4) methylation at -CpG- sites enhances meth-OH-PdG formation at codon 249; and 5) repair of meth-OH-PdG at codon 249 is poor...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28166970/effects-of-intrauterine-growth-restriction-during-late-pregnancy-on-the-cell-apoptosis-and-related-gene-expression-in-ovine-fetal-liver
#16
Yingchun Liu, Chi Ma, Hui Li, Lingyao Li, Feng Gao, Changjin Ao
This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver. Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.18 MJ ME kg BW(-0.75) d(-1), n = 6), Restricted Group 2 (RG2, 0.33 MJ ME kg BW(-0.75) d(-1), n = 6) and a Control Group (CG, ad libitum, 0.67 MJ ME kg BW (-0.75) d (-1), n = 6). Fetuses were recovered at slaughter on d 140...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28130345/the-piddosome-activates-p53-in-response-to-supernumerary-centrosomes
#17
Luca L Fava, Fabian Schuler, Valentina Sladky, Manuel D Haschka, Claudia Soratroi, Lisa Eiterer, Egon Demetz, Guenter Weiss, Stephan Geley, Erich A Nigg, Andreas Villunger
Centrosomes, the main microtubule-organizing centers in animal cells, are replicated exactly once during the cell division cycle to form the poles of the mitotic spindle. Supernumerary centrosomes can lead to aberrant cell division and have been causally linked to chromosomal instability and cancer. Here, we report that an increase in the number of mature centrosomes, generated by disrupting cytokinesis or forcing centrosome overduplication, triggers the activation of the PIDDosome multiprotein complex, leading to Caspase-2-mediated MDM2 cleavage, p53 stabilization, and p21-dependent cell cycle arrest...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28121078/research-highlights
#18
(no author information available yet)
In this issue, we highlight work from Cecchinato et al. revealing a technique for restoring chemotaxis in HIV-infected Th17 cells, a study by Wei et al. showing that Yersinia pestis YopM is an E3 ligase that can regulate host inflammasomes, a paper by Prokesch et al. reporting that p53 regulates metabolic adaptation to starvation in normal hepatocytes and work from Singh et al. that shows that Salmonella acquires nutrients from host cells by hijacking chaperone-mediated autophagy.
January 2017: FEBS Journal
https://www.readbyqxmd.com/read/28119452/microrna-375-is-induced-in-cisplatin-nephrotoxicity-to-repress-hepatocyte-nuclear-factor-1-%C3%AE
#19
Jielu Hao, Qiang Lou, Qingqing Wei, Shuqin Mei, Lin Li, Guangyu Wu, Qing-Sheng Mi, Changlin Mei, Zheng Dong
Nephrotoxicity is a major adverse effect of cisplatin-mediated chemotherapy in cancer patients. The pathogenesis of cisplatin-induced nephrotoxicity remains largely unclear, making it difficult to design effective renoprotective approaches. Here, we have examined the role of microRNAs (miRNAs) in cisplatin-induced nephrotoxicity. We show that cisplatin nephrotoxicity was not affected by overall depletion of both beneficial and detrimental miRNAs from kidney proximal tubular cells in mice in which the miRNA-generating enzyme Dicer had been conditionally knocked out...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28088184/anti-hepatitis-b-virus-hbv-response-of-imiquimod-based-toll-like-receptor-7-ligand-in-hbv-positive-human-hepatocelluar-carcinoma-cell-line
#20
Dipanwita Das, Isha Sengupta, Neelakshi Sarkar, Ananya Pal, Debraj Saha, Manikankana Bandopadhyay, Chandrima Das, Jimmy Narayan, Shivaram Prasad Singh, Sekhar Chakrabarti, Runu Chakravarty
BACKGROUND: Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. METHODS: The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837...
January 14, 2017: BMC Infectious Diseases
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