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https://www.readbyqxmd.com/read/29142165/possible-mechanism-for-the-polychlorinated-bipheny-linduced-liver-selective-accumulation-of-thyroxine-in-rats
#1
Yoshihisa Kato, Aki Fujii, Koichi Haraguchi, Yukiko Fujii, Kazutaka Atobe, Tetsuya Endo, Osamu Kimura, Nobuyuki Koga, Chiho Ohta, Shizuo Yamada, Masakuni Degawa
We have previously reported that decrease in level of serum thyroxine T4 by Kanechor 500 (KC500) in rats would occur through the increase in hepatic T4 accumulation rather than the increase in hepatic T4-glucuronyl transferase activity. In the present study, to understand the mechanism underlying the KC500-mediated increase in hepatic T4 accumulation, we examined the relationship between the KC500-mediated changes in hepatic T4 accumulation and the expression levels of mRNAs of hepatic transporters including T4 transporters...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29138286/transporter-expression-in-non-cancerous-and-cancerous-liver-tissue-from-donors-with-hepatocellular-carcinoma-and-chronic-hepatitis-c-infection-quantified-by-lc-ms-ms-proteomics
#2
Sarah Billington, Adrian S Ray, Laurent Salphati, Guangqing Xiao, Xiaoyan Chu, W Griffith Humphreys, Mingxiang Liao, Caroline A Lee, Anita A Mathias, Cornelis E C A Hop, Christopher Rowbottom, Raymond Evers, Yurong Lai, Edward J Kelly, Bhagwat Prasad, Jashvant D Unadkat
Protein expression of major hepatobiliary drug transporters (NTCP, OATPs, OCT1, BSEP, BCRP, MATE1, MRPs and P-gp) in cancerous (C, n=8) and adjacent non-cancerous (NC, n=33) liver tissues obtained from chronic hepatitis C patients with hepatocellular carcinoma (HCV-HCC) were quantified by LC-MS/MS proteomics. Herein, we compare our results with our previous data from non-infected non-cirrhotic (control, n=36) and HCV-cirrhotic (n=30) livers. The amount of membrane protein yielded from NC and C HCV-HCC tissues decreased (31%, 67%) relative to control livers...
November 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29128934/radiobiological-analysis-of-stereotactic-body-radiation-therapy-for-an-evidence-based-planning-target-volume-of-the-lung-using-multiphase-ct-images-obtained-with-a-pneumatic-abdominal-compression-apparatus-a-case-study
#3
Arun Chairmadurai, Harish Chandra Goel, Sandeep Kumar Jain, Pawan Kumar
This study evaluated the efficiency of stereotactic body radiation therapy of lung (SBRT-Lung) in generating a treatment volume using conventional multiple-phase three-dimensional computed tomography (3D-CT) of a patient immobilized with pneumatic abdominal compression. The institutional protocol for SBRT-Lung using the RapidArc technique relied on a planning target volume (PTV) delineated using 3D-CT and accounted for linear and angular displacement of the tumor during respiratory movements. The efficiency of the institutional protocol was compared with that of a conventional method for PTV delineation based on radiobiological estimates, such as tumor control probability (TCP) and normal tissue complication probability (NTCP), evaluated using dose-volume parameters...
November 11, 2017: Radiological Physics and Technology
https://www.readbyqxmd.com/read/29127322/reduced-hepatitis-b-and-d-viral-entry-using-clinically-applied-drugs-as-novel-inhibitors-of-the-bile-acid-transporter-ntcp
#4
Joanne M Donkers, Benno Zehnder, Gerard J P van Westen, Mark J Kwakkenbos, Adriaan P IJzerman, Ronald P J Oude Elferink, Ulrich Beuers, Stephan Urban, Stan F J van de Graaf
The sodium taurocholate co-transporting polypeptide (NTCP, SLC10A1) is the main hepatic transporter of conjugated bile acids, and the entry receptor for hepatitis B virus (HBV) and hepatitis delta virus (HDV). Myrcludex B, a synthetic peptide mimicking the NTCP-binding domain of HBV, effectively blocks HBV and HDV infection. In addition, Myrcludex B inhibits NTCP-mediated bile acid uptake, suggesting that also other NTCP inhibitors could potentially be a novel treatment of HBV/HDV infection. This study aims to identify clinically-applied compounds intervening with NTCP-mediated bile acid transport and HBV/HDV infection...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116221/establishment-of-a-fluorescent-in-situ-hybridization-assay-for-imaging-hepatitis-b-virus-nucleic-acids-in-cell-culture-models
#5
Xiaonan Zhang, Lei Yue, Zhanqing Zhang, Zhenghong Yuan
While chronic hepatitis B remains a global public health problem, the detailed spatiotemporal dynamics of the key molecular events leading to the multiplication and egress of hepatitis B virus (HBV) are still largely unclear. Previously, we developed a chromogenic in situ hybridization assay for detection of HBV RNA, DNA and covalently closed circular DNA in clinical liver biopsies. Here, we report the establishment of a fluorescent in situ hybridization method for the visualization of HBV RNA, HBV core particle DNA and intranuclear DNA in a tetracycline-inducible HBV replication system (HepAD38) and a de novo infection system (HepG2-NTCP)...
November 8, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29112762/alteration-of-bile-acid-and-cholesterol-biosynthesis-and-transport-by-perfluorononanoic-acid-pfna-in-mice
#6
Yue Zhang, Youcai Zhang, Curtis D Klaassen, Xingguo Cheng
Perfluorochemicals produce hepatotoxic effects via activation of PPARα and CAR nuclear receptors in animals. Bile formation is one major liver function. But it remains unknown whether perfluorochemicals alter metabolism of bile acids (BAs) in liver. The present study was designed to determine the impact of perfluorononanoic acid (PFNA) on BA and cholesterol homeostasis in mice. A single dose of PFNA (0.1 mmol/kg) was intraperitoneally administered to adult male wild-type (WT), PPARα-null, and CAR-null mice...
November 3, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29110732/normal-lung-sparing-tomotherapy-technique-in-stage-iii-lung-cancer
#7
Chae-Seon Hong, Sang Gyu Ju, Yong Chan Ahn, Gyu Sang Yoo, Jae Myoung Noh, Dongryul Oh, Kwangzoo Chung, Hongryull Pyo, Kwanghyun Jo
PURPOSE: Radiation pneumonitis (RP) has been a challenging obstacle in treating stage III lung cancer patients. Beam angle optimization (BAO) technique for Tomotherapy was developed to reduce the normal lung dose for stage III non-small cell lung cancer (NSCLC). Comparative analyses on plan quality by 3 different Intensity-modulated radiation therapy (IMRT) methods with BAO were done. MATERIALS AND METHODS: Ten consecutive stage IIIB NSCLC patients receiving linac-based static IMRT (L-IMRT) with total 66 Gy in 33 fractions to the PTV were selected...
November 6, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/29101415/target-tailoring-and-proton-beam-therapy-to-reduce-small-bowel-dose-in-cervical-cancer-radiotherapy-a-comparison-of-benefits
#8
Peter de Boer, Agustinus J A J van de Schoot, Henrike Westerveld, Mark Smit, Marrije R Buist, Arjan Bel, Coen R N Rasch, Lukas J A Stalpers
PURPOSE: The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). METHODS: The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI)...
November 3, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29089529/heparin-at-physiological-concentration-can-enhance-peg-free-in-vitro-infection-with-human-hepatitis-b-virus
#9
Gansukh Choijilsuren, Ren-Shiang Jhou, Shu-Fan Chou, Ching-Jen Chang, Hwai-I Yang, Yang-Yuan Chen, Wan-Long Chuang, Ming-Lung Yu, Chiaho Shih
Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29074078/the-impact-of-treatment-accuracy-on-proton-therapy-patient-selection-for-oropharyngeal-cancer-patients
#10
Tine Arts, Sebastiaan Breedveld, Martin A de Jong, Eleftheria Astreinidou, Lisa Tans, Fatma Keskin-Cambay, Augustinus D G Krol, Steven van de Water, Rik G Bijman, Mischa S Hoogeman
BACKGROUND AND PURPOSE: The impact of treatment accuracy on NTCP-based patient selection for proton therapy is currently unknown. This study investigates this impact for oropharyngeal cancer patients. MATERIALS AND METHODS: Data of 78 patients was used to automatically generate treatment plans for a simultaneously integrated boost prescribing 70 GyRBE/54.25 GyRBE in 35 fractions. IMRT treatment plans were generated with three different margins; intensity modulated proton therapy (IMPT) plans for five different setup and range robustness settings...
October 23, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29062118/propensity-score-matched-evaluation-of-the-incidence-of-radiation-pneumonitis-and-secondary-cancer-risk-for-breast-cancer-patients-treated-with-imrt-vmat
#11
Pei-Ju Chao, Hsiao-Fei Lee, Jen-Hong Lan, Shih-Sian Guo, Hui-Min Ting, Yu-Jie Huang, Hui-Chun Chen, Tsair-Fwu Lee
Propensity score matching evaluates the treatment incidence of radiation-induced pneumonitis (RP) and secondary cancer risk (SCR) after intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for breast cancer patients. Of 32 patients treated with IMRT and 58 who received VMAT were propensity matched in a 1:1 ratio. RP and SCR were evaluated as the endpoints of acute and chronic toxicity, respectively. Self-fitted normal tissue complication probability (NTCP) parameter values were used to analyze the risk of RP...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29060629/development-of-a-radiobiological-evaluation-tool-to-assess-the-expected-clinical-impacts-of-contouring-accuracy-between-manual-and-semi-automated-segmentation-algorithms
#12
Yusung Kim, Kaustubh Anil Patwardhan, Reinhard R Beichel, Brian J Smith, Christopher Mart, Kristin A Plichta, Tangel Chang, Milan Sonka, Michael M Graham, Vince Magnotta, Thomas Casavant, Junyi Xia, John M Buatti
RADEval is a tool developed to assess the expected clinical impact of contouring accuracy when comparing manual contouring and semi-automated segmentation. The RADEval tool, designed to process large scale datasets, imported a total of 2,760 segmentation datasets, along with a Simultaneous Truth and Performance Level Estimation (STAPLE) to act as ground truth tumor segmentations. Virtual dose-maps were created within RADEval and two different tumor control probability (TCP) values using a Logistic and a Poisson TCP models were calculated in RADEval using each STAPLE and each dose-map...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29059468/hepatitis-b-virus-sensitivity-to-interferon-%C3%AE-in-hepatocytes-is-more-associated-with-cellular-interferon-response-than-with-viral-genotype
#13
Fang Shen, Yaming Li, Yang Wang, Vitina Sozzi, Peter A Revill, Jiangxia Liu, Lu Gao, Guang Yang, Mengji Lu, Kathrin Sutter, Ulf Dittmer, Jieliang Chen, Zhenghong Yuan
Interferon-α (IFN-α) is used to treat chronic HBV infection but only 20-40% of patients respond well. Clinical observations have suggested that HBV genotype is associated with the response to IFN therapy, however, its role in viral responsiveness to IFN in HBV-infected hepatocytes remain unclear. Here, we produced infectious virions of HBV genotypes A to D to infect three well-recognized cell culture-based HBV infection systems including primary human hepatocytes (PHH), differentiated HepaRG (dHepaRG) and HepG2-NTCP cells to quantitatively compare the antiviral effect of IFN-α on HBV across genotypes and cell models...
October 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29050954/the-trendy-multi-center-randomized-trial-on-hepatocellular-carcinoma-trial-qa-including-automated-treatment-planning-and-benchmark-case-results
#14
Steven J M Habraken, Abdul Wahab M Sharfo, Jeroen Buijsen, Wilko F A R Verbakel, Cornelis J A Haasbeek, Michel C Öllers, Henrike Westerveld, Niek van Wieringen, Onne Reerink, Enrica Seravalli, Pètra M Braam, Markus Wendling, Thomas Lacornerie, Xavier Mirabel, Reinhilde Weytjens, Lieselotte Depuydt, Stephanie Tanadini-Lang, Oliver Riesterer, Karin Haustermans, Tom Depuydt, Roy S Dwarkasing, François E J A Willemssen, Ben J M Heijmen, Alejandra Méndez Romero
BACKGROUND AND PURPOSE: The TRENDY trial is an international multi-center phase-II study, randomizing hepatocellular carcinoma (HCC) patients between transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality assurance (QA) program, including prospective plan feedback based on automated treatment planning, is described and results are reported. MATERIALS AND METHODS: Scans of a single patient were used as a benchmark case...
October 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29037095/biological-dose-and-complication-probabilities-for-the-rectum-and-bladder-based-on-linear-energy-transfer-distributions-in-spot-scanning-proton-therapy-of-prostate-cancer
#15
Jesper Pedersen, Jørgen B B Petersen, Camilla H Stokkevåg, Kristian S Ytre-Hauge, Stella Flampouri, Zuofeng Li, Nancy Mendenhall, Ludvig P Muren
BACKGROUND: The increased linear energy transfer (LET) at the end of the Bragg peak causes concern for an elevated and spatially varying relative biological effectiveness (RBE) of proton therapy (PT), often in or close to dose-limiting normal tissues. In this study, we investigated dose-averaged LET (LETd) distributions for spot scanning PT of prostate cancer patients using different beam angle configurations. In addition, we derived RBE-weighted (RBEw) dose distributions and related normal tissue complication probabilities (NTCPs) for the rectum and bladder...
November 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29034482/deep-reinforcement-learning-for-automated-radiation-adaptation-in-lung-cancer
#16
Huan-Hsin Tseng, Yi Luo, Sunan Cui, Jen-Tzung Chien, Randall K Ten Haken, Issam El Naqa
PURPOSE: To investigate deep reinforcement learning (DRL) based on historical treatment plans for developing automated radiation adaptation protocols for non-small cell lung cancer (NSCLC) patients that aim to maximize tumor local control at reduced rates of radiation pneumonitis grade 2 (RP2). METHODS: In a retrospective population of 114 NSCLC patients who received radiotherapy, a 3-component neural networks framework was developed for deep reinforcement learning (DRL) of dose fractionation adaptation...
October 16, 2017: Medical Physics
https://www.readbyqxmd.com/read/29024779/kinetic-characterization-of-bile-salt-transport-by-human-ntcp-slc10a1
#17
Márton Jani, Erzsébet Beéry, Teresa Heslop, Beáta Tóth, Bhavana Jagota, Emese Kis, B Kevin Park, Peter Krajcsi, Richard J Weaver
The transport of bile acids facilitated by NTCP is an important factor in establishing bile flow. In this study, we examine the kinetics associated with human NTCP-dependent transport of two quantitatively important bile acids comprising the human bile acid pool, chenodeoxycholic acid and glycine-chenodeoxycholate, and secondary bile salt, 3-sulfo-glycolithocholate of potential toxicological significance. The study employed human NTCP overexpressing Chinese Hamster Ovary cells and results compared with taurocholate, a prototypical bile salt commonly used in transporter studies...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28987596/computational-discovery-and-experimental-verification-of-farnesoid-x-receptor-agonist-auraptene-to-protect-against-cholestatic-liver-injury
#18
Xiaoguang Gao, Ting Fu, Changyuan Wang, Chenqing Ning, Yulong Kong, Zhihao Liu, Huijun Sun, Xiaodong Ma, Kexin Liu, Qiang Meng
Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a novel therapeutic strategy against cholestasis. Herein, we used a novel computational strategy with two-dimensional virtual screening for FXR agonists. For the first time, we found that auraptene (AUR), a natural product, can activate FXR to exert hepatoprotective effect against cholestatic liver injury in vivo and in vitro. Importantly, AUR was found to significantly decrease the mortality of cholestatic mice...
October 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28973556/clofibrate-decreases-bile-acids-in-livers-of-male-mice-by-increasing-biliary-bile-acid-excretion-in-a-ppar%C3%AE-dependent-manner
#19
Youcai Zhang, Andrew J Lickteig, Iván L Csanaky, Curtis D Klaassen
Fibrates and their receptor, namely peroxisome proliferator-activated receptor α (PPARα), have been reported to regulate bile acid (BA) synthesis and transport. However, the effect of fibrate treatment and PPARα activation on BA homeostasis remains controversial. In the present study, both wild-type (WT) and PPARα-null male mice were treated with clofibrate (CLOF) for 4 days to evaluate the effects of short-term PPARα activation on bile acid (BA) homeostasis. While a decrease in total BAs was observed in livers of CLOF-treated WT mice, it was not observed in PPARα-null mice...
September 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28967273/normal-tissue-complication-probability-modeling-of-radiation-induced-sensorineural-hearing-loss-after-head-and-neck-radiation-therapy
#20
Susan Cheraghi, Alireza Nikoofar, Mohsen Bakhshandeh, Samideh Khoei, Saeid Farahani, Hamid Abdollahi, Seied Rabi Mahdavi
PURPOSE: The aim of this study was to generate the dose-response curves by six normal tissue complication probability (NTCP) models and ranking the models for prediction of radiation induced sensorineural hearing loss (SNHL) caused by head and neck radiation therapy (RT). METHODS AND MATERIALS: Pure tone audiometry (PTA) was performed on 70 ears of patients for 12 months after the completion of radiation therapy. The SNHL was defined as a threshold shift ≤15 dB at 2 contiguous frequencies according to the common toxicity criteria for adverse events scoring system...
October 2, 2017: International Journal of Radiation Biology
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