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https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#1
Ursula J Lemberger, Claudia Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890789/cyclosporin-derivatives-inhibit-hepatitis-b-virus-entry-without-interfering-the-ntcp-transporter
#2
Satomi Shimura, Koichi Watashi, Kento Fukano, Michael Peel, Ann Sluder, Fumihiro Kawai, Masashi Iwamoto, Senko Tsukuda, Junko S Takeuchi, Takeshi Miyake, Masaya Sugiyama, Yuki Ogasawara, Sam-Yong Park, Yasuhito Tanaka, Hiroyuki Kusuhara, Masashi Mizokami, Camille Sureau, Takaji Wakita
BACKGROUND&AIMS: Most of the specific inhibitors of hepatitis B virus (HBV) entry, including myrcludex-B and cyclosporin A (CsA), target an HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). As all these agents have capacities to impair the NTCP transporter activity for bile acid uptake and thus may cause significant adverse effects, we aim to identify small molecules that inhibit HBV entry but least affecting the NTCP transporter function. METHODS: We focused on derivatives of CsA, which originally inhibited both HBV entry and NTCP-mediated bile acid uptake, to analyze the possibility to distinguish these two activities...
November 24, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27882152/clinical-and-molecular-study-of-a-pediatric-patient-with-sodium-taurocholate-cotransporting-polypeptide-deficiency
#3
Mei Deng, Man Mao, Li Guo, Feng-Ping Chen, Wang-Rong Wen, Yuan-Zong Song
The human solute carrier family 10 member 1 (SLC10A1) gene encodes sodium taurocholate cotransporting polypeptide (NTCP), the principal transporter of conjugated bile salts from the plasma into hepatocytes. Although the function of NTCP has been studied extensively and a number of SLC10A1 variations have been identified in humans, information regarding NTCP deficiency is limited. To date, only one patient with NTCP deficiency has been described; however, in the present study a pediatric patient who experienced intractable and striking hypercholanemia is presented...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27863453/a-new-class-of-hepatitis-b-and-d-virus-entry-inhibitors-proanthocyanidin-and-its-analogs-that-directly-act-on-the-viral-large-surface-proteins
#4
Senko Tsukuda, Koichi Watashi, Taichi Hojima, Masanori Isogawa, Masashi Iwamoto, Katsumi Omagari, Ryosuke Suzuki, Hideki Aizaki, Soichi Kojima, Masaya Sugiyama, Akiko Saito, Yasuhito Tanaka, Masashi Mizokami, Camille Sureau, Takaji Wakita
: Introduction of direct acting antivirals against hepatitis C virus (HCV) has provided a revolutionary improvement in the treatment outcome. In contrast to HCV, however, the strategy for developing new antiviral agents against hepatitis B virus (HBV), especially viral-targeting compounds, is limited since HBV requires only four viral genes for its efficient replication/infection. Here, we identify an oligomeric flavonoid, proanthocyanidin (PAC) and its analogs, which inhibit HBV entry into host cells by targeting the HBV large surface protein (LHBs)...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27847266/the-dosimetric-and-radiobiological-impact-of-calculation-grid-size-on-head-and-neck-imrt
#5
Shiv P Srivastava, Chee-Wai Cheng, Indra J Das
PURPOSE: Small-volume structures usually found in the head and neck may be susceptible to dose-volume averaging, which has not been studied. Here, the impact of calculation grid size on dose distribution for tumor control probability (TCP) and normal tissue complication probability (NTCP) is investigated for head and neck (H&N) intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: IMRT plans were generated for H&N patients with different grid sizes (1-5 mm) to calculate dose and related TCP and NTCP...
October 11, 2016: Practical Radiation Oncology
https://www.readbyqxmd.com/read/27818225/protective-effects-of-srt1720-via-the-hnf1%C3%AE-fxr-signalling-pathway-and-anti-inflammatory-mechanisms-in-mice-with-estrogen-induced-cholestatic-liver-injury
#6
Linxi Yu, Xiaoxin Liu, Xiaojiaoyang Li, Zihang Yuan, Hang Yang, Luyong Zhang, Zhenzhou Jiang
Sirtuin 1 (SIRT1) is the most conserved mammalian NAD(+)-dependent protein deacetylase and is a member of the silent information regulator 2 (Sir2) families of proteins (also known as Sirtuins). In the liver, hepatic SIRT1 modulates bile acid metabolism through the regulation of farnesoid X receptor (FXR) expression. FXR is one of the most important nuclear receptors involved in the regulation of bile acid metabolism. SIRT1 modulates the FXR expression at multiple levels, including direct deacetylation of this transcription factor and transcriptional regulation through hepatocyte nuclear factor 1α (HNF1α)...
November 3, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27815805/lumbar-sacral-bone-marrow-dose%C3%A2-modeling-for-acute-hematological-toxicity-in-anal-cancer-patients-treated-with-concurrent-chemo-radiation
#7
Pierfrancesco Franco, Riccardo Ragona, Francesca Arcadipane, Massimiliano Mistrangelo, Paola Cassoni, Nadia Rondi, Mario Morino, Patrizia Racca, Umberto Ricardi
The aim of the study was to model acute hematologic toxicity (HT) and dose to pelvic osseous structures in anal cancer patients treated with definitive chemo-radiation (CT-RT). A total of 53 patients receiving CT-RT were analyzed. Pelvic bone marrow and corresponding subsites were contoured: ilium, lower pelvis and lumbosacral spine (LSBM). Dose-volume histograms points and mean doses were collected. Logistic regression was performed to correlate dosimetric parameters and ≥G3 HT as endpoint. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model...
December 2016: Medical Oncology
https://www.readbyqxmd.com/read/27806610/on-the-new-metrics-for-imrt-qa-verification
#8
Alejandro Garcia-Romero, Araceli Hernandez-Vitoria, Esther Millan-Cebrian, Veronica Alba-Escorihuela, Sonia Serrano-Zabaleta, Pablo Ortega-Pardina
PURPOSE: The aim of this work is to search for new metrics that could give more reliable acceptance/rejection criteria on the IMRT verification process and to offer solutions to the discrepancies found among different conventional metrics. Therefore, besides conventional metrics, new ones are proposed and evaluated with new tools to find correlations among them. These new metrics are based on the processing of the dose-volume histogram information, evaluating the absorbed dose differences, the dose constraint fulfillment, or modified biomathematical treatment outcome models such as tumor control probability (TCP) and normal tissue complication probability (NTCP)...
November 2016: Medical Physics
https://www.readbyqxmd.com/read/27806340/dosimetric-factors-and-lyman-normal-tissue-complication-modelling-analysis-for-predicting-radiation-induced-lung-injury-in-postoperative-breast-cancer-radiotherapy-a-prospective-study
#9
Zhi-Rui Zhou, Qing Han, Shi-Xiong Liang, Xiao-Dong He, Nu-Yun Cao, Ying-Jie Zi
To investigate the relationship between dosimetric factors, including Lyman normal-tissue complication (NTCP) parameters and radiation-induced lung injury (RILI), in postoperative breast cancer patients treated by intensity modulated radiotherapy (IMRT). 109 breast cancer patients who received IMRT between January 2012 and December 2013 were prospectively enrolled. A maximum likelihood analysis yielded the best estimates for Lyman NTCP parameters. Ten patients were diagnosed with RILI (primarily Grade 1 or Grade 2 RILI); the rate of RILI was 9...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27784961/elucidation-of-the-early-infection-machinery-of-hepatitis-b-virus-by-using-bio-nanocapsule
#10
REVIEW
Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda
Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV...
October 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27783949/solute-carrier-ntcp-regulates-innate-antiviral-immune-responses-targeting-hepatitis-c-virus-infection-of-hepatocytes
#11
Eloi R Verrier, Che C Colpitts, Charlotte Bach, Laura Heydmann, Laetitia Zona, Fei Xiao, Christine Thumann, Emilie Crouchet, Raphaël Gaudin, Camille Sureau, François-Loïc Cosset, Jane A McKeating, Patrick Pessaux, Yujin Hoshida, Catherine Schuster, Mirjam B Zeisel, Thomas F Baumert
Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27783675/dna-polymerase-%C3%AE%C2%BA-is-a-key-cellular-factor-for-the-formation-of-covalently-closed-circular-dna-of-hepatitis-b-virus
#12
Yonghe Qi, Zhenchao Gao, Guangwei Xu, Bo Peng, Chenxuan Liu, Huan Yan, Qiyan Yao, Guoliang Sun, Yang Liu, Dingbin Tang, Zilin Song, Wenhui He, Yinyan Sun, Ju-Tao Guo, Wenhui Li
Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27780695/real-time-image-guided-adaptive-predictive-prostate-radiotherapy-using-rectal-diameter-as-a-predictor-of-motion
#13
R Oates, A Brown, A Tan, F Foroudi, M Lim Joon, M Schneider, A Herschtal, T Kron
AIMS: To investigate a relationship between maximum rectal diameter (MRD) on pre-treatment cone beam computed tomography (CBCT) and intra-fraction prostate motion, in the context of an adaptive image-guided radiotherapy (IGRT) method. MATERIALS AND METHODS: The MRD was measured on 2125 CBCTs from 55 retrospective patient datasets and related to prostate displacement from intra-fraction imaging. A linear regression model was developed to determine a threshold MRD associated with a high probability of small prostate displacement...
October 22, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/27769262/a-treatment-planning-study-of-proton-arc-therapy-for-para-aortic-lymph-node-tumors-dosimetric-evaluation-of-conventional-proton-therapy-proton-arc-therapy-and-intensity-modulated-radiotherapy
#14
Jeong-Eun Rah, Gwe-Ya Kim, Do Hoon Oh, Tae Hyun Kim, Jong Won Kim, Dae Yong Kim, Sung Yong Park, Dongho Shin
BACKGROUND: The purpose of this study is to evaluate the dosimetric benefits of a proton arc technique for treating tumors of the para-aortic lymph nodes (PALN). METHOD: In nine patients, a proton arc therapy (PAT) technique was compared with intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) techniques with respect to the planning target volume (PTV) and organs at risk (OAR). PTV coverage, conformity index (CI), homogeneity index (HI) and OAR doses were compared...
October 21, 2016: Radiation Oncology
https://www.readbyqxmd.com/read/27765674/both-cholestatic-and-steatotic-drugs-trigger-extensive-alterations-in-the-mrna-level-of-biliary-transporters-in-rat-hepatocytes-application-to-develop-new-predictive-biomarkers-for-early-drug-development
#15
M Teresa Donato, Mireia López-Riera, José V Castell, María J Gómez-Lechón, Ramiro Jover
Disruption of the vectorial bile acid transport in the liver is a key feature of cholestatic drugs, although many causal and mechanistic aspects are still unknown. The aim of the present study was to explore if cholestatic drugs can repress or induce the expression of hepatic transporters. To this end, sandwich-cultured rat hepatocytes were treated with cholestatic and non-cholestatic (steatotic, non-hepatotoxic, etc.) drugs and the mRNA expression of 10 uptake and efflux biliary transporters was measured. Results evidenced that all cholestatic drugs cause extensive alterations in the mRNA expression of most biliary transporters...
October 17, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27756364/dose-response-effect-of-berberine-on-bile-acid-profile-and-gut-microbiota-in-mice
#16
Ying Guo, YouCai Zhang, WeiHua Huang, Felcy Pavithra Selwyn, Curtis D Klaassen
BACKGROUND: Berberine (BBR) is a traditional antimicrobial herbal medicine. Recently, BBR has gained popularity as a supplement to lower blood lipids, cholesterol and glucose. Bile acids (BAs) are known to regulate blood levels of triglycerides, cholesterol, glucose and energy homeostasis, and gut flora play an important role in BA metabolism. However, whether BBR alters BAs metabolism or dose-response effect of BBR on gut flora is unknown. METHODS: In this study, the effects of various doses of BBR on the concentrations of BAs in liver and serum of male C57BL/6 mice were determined by UPLC-MS/MS, and the expression of BA-related genes, as well as the amount of 32 of the most abundant gut bacterial species in the terminal ileum and large intestine of male C57BL/6 mice were quantified by RT-PCR and Quantigene 2...
October 18, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27751618/bladder-radiotherapy-treatment-a-retrospective-comparison-of-3-dimensional-conformal-radiotherapy-intensity-modulated-radiation-therapy-and-volumetric-modulated-arc-therapy-plans
#17
Katia Pasciuti, Shrinivas Kuthpady, Anne Anderson, Bronagh Best, Saleem Waqar, Subhra Chowdhury
To examine tumor׳s and organ׳s response when different radiotherapy plan techniques are used. Ten patients with confirmed bladder tumors were first treated using 3-dimensional conformal radiotherapy (3DCRT) and subsequently the original plans were re-optimized using the intensity-modulated radiation treatment (IMRT) and volumetric-modulated arc therapy (VMAT)-techniques. Targets coverage in terms of conformity and homogeneity index, TCP, and organs׳ dose limits, including integral dose analysis were evaluated...
October 14, 2016: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/27741379/dosimetric-and-radiobiological-impact-of-intensity-modulated-proton-therapy-and-rapidarc-planning-for-high-risk-prostate-cancer-with-seminal-vesicles
#18
Suresh Rana, ChihYao Cheng, Li Zhao, SungYong Park, Gary Larson, Carlos Vargas, Megan Dunn, Yuanshui Zheng
INTRODUCTION: The purpose of this study was to evaluate the dosimetric and radiobiological impact of intensity modulated proton therapy (IMPT) and RapidArc planning for high-risk prostate cancer with seminal vesicles. METHODS: Ten high-risk prostate cancer cases were included in this retrospective study. For each case, IMPT plans were generated using multiple field optimisation (MFO) technique (two fields) with XiO treatment planning system (TPS), whereas RapidArc plans were generated using double-arc technique (two full arcs) with Eclipse TPS...
May 11, 2016: Journal of Medical Radiation Sciences
https://www.readbyqxmd.com/read/27737931/inhibition-of-intestinal-oatp2b1-results-in-a-significant-drug-drug-interaction-by-causing-a-two-fold-decrease-in-exposure-of-rosuvastatin
#19
Marta Johnson, Dipal R Patel, Christopher J Matheny, May Y K Ho, Liangfu Chen, Harma Ellens
Rosuvastatin is a widely prescribed anti-hyperlipidemic which undergoes limited metabolism, but is an in vitro substrate of multiple transporters (OATP1B1, OATP1B3, OATP1A2, OATP2B1, NTCP, BCRP, MRP2, MRP4, OAT3). It is therefore frequently used as probe substrate in clinical drug-drug interaction (DDI) studies to investigate transporter inhibition. While each of these transporters is believed to play a role in rosuvastatin disposition, multiple pharmacogenetic studies confirm that OATP1B1 and BCRP play an important role in vivo...
October 13, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27709077/correlation-between-pneumonitis-risk-in-radiation-oncology-and-lung-density-measured-with-x-ray-computed-tomography
#20
Abdulhamid Chaikh, Jacques Balosso
BACKGROUND: The risk of toxicity with radiation oncology for lung cancer limits the maximal radiation dose that can be delivered to thoracic tumors. This study aims at investigating the correlation between normal tissue complication probability (NTCP) and physical lung density by analyzing the computed tomography (CT) scan imaging used for radiotherapy dose planning. METHODS: Data from CT of lung cancer patients (n=10), treated with three dimensional radiotherapy, were selected for this study...
August 2016: Quantitative Imaging in Medicine and Surgery
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