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https://www.readbyqxmd.com/read/28920500/acute-toxicity-of-the-bowel-after-stereotactic-robotic-radiotherapy-for-abdominopelvic-oligometastases
#1
Michael Frelinghuysen, Wilco Schillemans, Lieke Hol, Cornelis Verhoef, Mischa Hoogeman, Joost Jan Nuyttens
AIM: To correlate dose-volume histogram (DVH) parameters with appearance of grade ≥2 acute and late gastrointestinal toxicity of stereotactic body radiotherapy (SBRT) in patients with abdominopelvic solitary or oligometastatic disease outside the liver. MATERIAL AND METHODS: Acute and late bowel toxicity of 84 abdominopelvic oligometastatic patients was registered. A logistic regression was performed between different DVH parameters and presence of grade ≥2 acute and late toxicity...
September 18, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28919113/hepatic-tmem30a-deficiency-causes-intrahepatic-cholestasis-by-impairing-expression-and-localization-of-bile-salt-transporters
#2
Leiming Liu, Lingling Zhang, Lin Zhang, Fan Yang, Xudong Zhu, Zhongjie Lu, Yeming Yang, Haiqi Lu, Lifeng Feng, Zhuo Wang, Hui Chen, Sheng Yan, Lin Wang, Zhenyu Ju, Hongchuan Jin, Xianjun Zhu
Mutations in ATP8B1 or ATP11C (members of P4-type ATPases) cause progressive familial intrahepatic cholestasis type 1 (PFIC1) in human or intrahepatic cholestasis in mice. Transmembrane protein 30A (TMEM30A), as a β-subunit, is essential for the function of P4-type ATPases including ATP8B1 and ATP11C, however, its role in the etiology of cholestasis remains poorly understood. To investigate the function of TMEM30A in bile salt homeostasis, we developed Tmem30a liver-specific knockout (LKO) mice. Tmem30a LKO mice suffered from hyperbilirubinaemia, hypercholanaemia, inflammatory infiltration, ductular proliferation and liver fibrosis...
September 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28918679/relating-the-proton-relative-biological-effectiveness-to-tumor-control-and-normal-tissue-complication-probabilities-assuming-interpatient-variability-in-%C3%AE-%C3%AE
#3
Harald Paganetti
BACKGROUND: Proton therapy uses a constant relative biological effectiveness (RBE) of 1.1. The use of variable RBE values has been suggested but is currently not feasible due to uncertainties. The impact of variable RBE has solely been studied using dosimetric indices. This work elucidates the impact of RBE variations on tumor control and normal tissue complication probabilities (TCP/NTCP). METHODS: Models to estimate TCP and NTCP were used in combination with an empirical proton RBE model...
September 18, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28915572/down-regulation-of-ntcp-expression-by-cyclin-d1-in-hepatitis-b-virus-related-hepatocellular-carcinoma-has-clinical-significance
#4
Jingting Kang, Jie Wang, Jin Cheng, Zhiliang Cao, Ran Chen, Huiyu Li, Shuang Liu, Xiangmei Chen, Jianhua Sui, Fengmin Lu
The sodium-dependent taurocholate cotransporter polypeptide (NTCP) has been identified as a liver specific functional receptor for the hepatitis B virus (HBV). Previous studies indicated that the expression of NTCP may be associated with the proliferation status of hepatocytes. However, the involvement of NTCP in hepatocellular carcinoma (HCC) cells proliferation remains unclear. In this study, we confirmed that NTCP was down-regulated in HCC tumor tissues compared with that in the adjacent non-tumor tissues (P < 0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887167/identification-of-slug-and-sox7-as-transcriptional-repressors-binding-to-the-hepatitis-b-virus-core-promoter
#5
Hui Ling Ko, Tze Hau Lam, Huijin Ng, Jiaying Toh, Liang Wei Wang, Ee Chee Ren
BACKGROUND & AIMS: The Hepatitis B Virus (HBV) is carried in many non-liver cell types but does not actively replicate in them. We investigated the possibility that these cells possess HBVCP transcription inhibitory mechanisms specifically absent in liver cells, which together with other liver-specific mechanisms such as NTCP-mediated entry, enable liver cells to effectively produce HBV. METHODS: Liver and non-liver cell lines were screened for their capacity to activate the HBVCP and synthesize pgRNA...
September 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28884310/radiation-induced-acute-dysphagia-prospective-observational-study-on-42%C3%A2-head-and-neck-cancer-patients
#6
D Alterio, M A Gerardi, L Cella, R Spoto, V Zurlo, A Sabbatini, C Fodor, V D'Avino, M Conson, F Valoriani, D Ciardo, R Pacelli, A Ferrari, P Maisonneuve, L Preda, R Bruschini, M Cossu Rocca, E Rondi, S Colangione, G Palma, S Dicuonzo, R Orecchia, G Sanguineti, B A Jereczek-Fossa
PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis...
September 7, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28871982/evaluating-the-toxicity-reduction-with-computed-tomographic-ventilation-functional-avoidance-radiation-therapy
#7
Austin M Faught, Yuya Miyasaka, Noriyuki Kadoya, Richard Castillo, Edward Castillo, Yevgeniy Vinogradskiy, Tokihiro Yamamoto
PURPOSE: Computed tomographic (CT) ventilation imaging is a new modality that uses 4-dimensional (4D) CT information to calculate lung ventilation. Although retrospective studies have reported on the reduction in dose to functional lung, no work to our knowledge has been published in which the dosimetric improvements have been translated to a reduction in the probability of pulmonary toxicity. Our work estimates the reduction in toxicity for CT ventilation-based functional avoidance planning...
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28867436/effects-of-diosmetin-on-nine-cytochrome-p450-isoforms-ugts-and-three-drug-transporters-in-vitro
#8
Jun-Jun Chen, Jing-Xian Zhang, Xiang-Qi Zhang, Mei-Juan Qi, Mei-Zhi Shi, Jiao Yang, Ke-Zhi Zhang, Cheng Guo, Yong-Long Han
Diosmetin (3', 5, 7-trihydroxy-4'-methoxyflavone), a natural flavonoid from traditional Chinese herbs, has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic and anti-inflammatory activity. However, flavonoids could affect the metabolic enzymes and cause drug-drug interactions (DDI), reducing the efficacy of co-administered drugs and potentially resulting in serious adverse reactions. To evaluate its potential to interact with co-administered drugs, the IC50 value of phase I cytochrome P450 enzymes (CYPs), phase II UDP-glucuronyltransferases (UGTs) and hepatic uptake transporters (organic cation transporters (OCTs), organic anion transporter polypeptides (OATPs) and Na(+)-taurocholate cotransporting polypeptides (NTCPs)) were examined in vitro by LC-MS/MS...
September 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28858854/photon-iso-effective-dose-for-cancer-treatment-with-mixed-field-radiation-based-on-dose-response-assessment-from-human-and-an-animal-model-clinical-application-to-boron-neutron-capture-therapy-for-head-and-neck-cancer
#9
Sara Josefina Gonzalez, Emiliano C C Pozzi, Andrea Monti Hughes, Lucas Provenzano, Hanna Koivunoro, Daniel Germán Carando, Silvia Inés Thorp, Mariana Rosalía Casal, Silva Bortolussi, Verónica A Trivillin, Marcela A Garabalino, Paula Curotto, Elisa M Heber, Gustavo A Santa Cruz, Leena Kankaanranta, Heikki Joensuu, Amanda E Schwint
Boron Neutron Capture Therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans...
August 31, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28835676/homozygous-p-ser267phe-in-slc10a1-is-associated-with-a-new-type-of-hypercholanemia-and-implications-for-personalized-medicine
#10
Ruihong Liu, Chuming Chen, Xuefeng Xia, Qijun Liao, Qiong Wang, Paul J Newcombe, Shuhua Xu, Minghui Chen, Yue Ding, Xiaoying Li, Zhihong Liao, Fucheng Li, Minlian Du, Huaiqiu Huang, Ruimin Dong, Weiping Deng, Ye Wang, Binghui Zeng, Qihao Pan, Danhua Jiang, Hao Zeng, Pak Sham, Yingnan Cao, Patrick H Maxwell, Zhi-Liang Gao, Liang Peng, Yiming Wang
SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids (BAs) and the receptor for hepatitis B and D viruses. NTCP is also a target of multiple drugs. We aimed to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1. We identified eight individuals with homozygous p.Ser267Phe mutation in SLC10A1 and followed up for 8-90 months. We compared their total serum BAs and 6 species of BAs with 170 wild-type and 107 heterozygous healthy individuals...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830219/optimisation-of-radiotherapy-fractionation-schedules-based-on-radiobiological-functions
#11
Fernando Pizarro, Araceli Hernández
OBJECTIVE: To present a method for optimising radiotherapy fractionation schedules using radiobiological tools and taking into account the patient's dose-volume histograms (DVH). METHODS: This method uses a figure of merit based on the uncomplicated tumour control probability (P+) and the generalised equivalent uniform dose (gEUD). A set of doses per fraction is selected in order to find the dose per fraction and the total dose, thus maximising the figure of merit and leading to a biologically effective dose that is similar to the prescribed schedule...
August 22, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28828923/impact-of-model-and-dose-uncertainty-on-model-based-selection-of-oropharyngeal-cancer-patients-for-proton-therapy
#12
Rik G Bijman, Sebastiaan Breedveld, Tine Arts, Eleftheria Astreinidou, Martin A de Jong, Patrick V Granton, Steven F Petit, Mischa S Hoogeman
BACKGROUND: Proton therapy is becoming increasingly available, so it is important to apply objective and individualized patient selection to identify those who are expected to benefit most from proton therapy compared to conventional intensity modulated radiation therapy (IMRT). Comparative treatment planning using normal tissue complication probability (NTCP) evaluation has recently been proposed. This work investigates the impact of NTCP model and dose uncertainties on model-based patient selection...
August 22, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28826308/the-influence-of-breathing-motion-and-a-variable-relative-biological-effectiveness-in-proton-therapy-of-left-sided-breast-cancer
#13
Jakob Ödén, Iuliana Toma-Dasu, Kjell Eriksson, Anna Maria Flejmer, Alexandru Dasu
BACKGROUND: Proton breast radiotherapy has been suggested to improve target coverage as well as reduce cardiopulmonary and integral dose compared with photon therapy. This study aims to assess this potential when accounting for breathing motion and a variable relative biological effectiveness (RBE). METHODS: Photon and robustly optimized proton plans were generated to deliver 50 Gy (RBE) in 25 fractions (RBE = 1.1) to the CTV (whole left breast) for 12 patients...
August 22, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28806990/dvh-and-ntcp-based-dosimetric-comparison-of-different-longitudinal-margins-for-vmat-imrt-of-esophageal-cancer
#14
S Münch, M Oechsner, S E Combs, D Habermehl
PURPOSE: To cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3-4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2-3 cm might be reasonable when advanced diagnostic imaging is integrated into target volume delineation. Purpose of this study was to compare the dose distribution and deposition to the organs at risk (OAR) for different longitudinal margins using a DVH- and NTCP-based approach. METHODS: Ten patients with SCC of the middle or lower third were retrospectively selected...
August 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28802063/hepatitis-b-virus-pregenomic-rna-in-hepatocellular-carcinoma-a-nosological-and-prognostic-determinant
#15
Boris Halgand, Christophe Desterke, Lise Rivière, Guillaume Fallot, Mylène Sebagh, Julien Calderaro, Paulette Bioulac-Sage, Christine Neuveut, Marie-Annick Buendia, Didier Samuel, Cyrille Féray
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). However, very little is known about the replication of HBV in HCC tissues. PATIENTS AND METHODS: We analysed viral and cellular parameters in HCC (T) and non-tumor liver (NT) samples from 99 HBsAg-positive, virologically suppressed patients treated by tumour resection or liver transplantation. We examined total HBV DNA and RNA as well as covalently closed circular DNA (cccDNA) and pregenomic RNA (pgRNA), which are considered as markers of active HBV replication...
August 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28800539/development-of-a-rapid-and-sensitive-multiple-reaction-monitoring-proteomic-approach-for-quantification-of-transporters-in-human-liver-tissue
#16
Li Wang, Kasi J Rubadue, Jeffrey Alberts, David W Bedwell, Kenneth J Ruterbories
With increasing knowledge on the role of hepatic transporters in drug disposition, numerous efforts have been described to quantify the expression of human hepatic transporters. However, reported quantitative proteomic approaches often require long analysis times. Additionally, greater assay sensitivity is still necessary for less abundant transporters or limited quantity of samples (e.g. hepatocytes and liver tissue). In the present study, an LC-MS/MS method for rapid and simultaneous quantification of 12 hepatic transporters (BCRP, BSEP, MATE1, MRP2, MRP3, MRP4, NTCP, OATP1B1, 1B3, 2B1, OCT1, and P-gp) was developed...
September 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28794147/erratum-the-rs2296651-s267f-variant-on-ntcp-slc10a1-is-inversely-associated-with-chronic-hepatitis-b-and-progression-to-cirrhosis-and-hepatocellular-carcinoma-in-patients-with-chronic-hepatitis-b
#17
https://www.readbyqxmd.com/read/28741221/optimization-and-application-of-a-biotinylation-method-for-quantification-of-plasma-membrane-expression-of-transporters-in-cells
#18
Vineet Kumar, Tot Bui Nguyen, Beáta Tóth, Viktoria Juhasz, Jashvant D Unadkat
Quantitative proteomics, using LC-MS/MS, is increasingly used to quantify drug transporters present in tissues and cells. Most of these investigations quantify total transporter expression in the cells by utilizing a total membrane fraction, not only the plasma membrane. Here, we report development and optimization of a biotinylation method to quantify protein expression of transporters in the plasma membrane of cells. The Pierce cell surface isolation protocol was optimized for plasma membrane isolation. Incubation of OATP1B1-expressing CHO cells with 0...
July 24, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28734962/analyzing-the-hepatoprotective-effect-of-the-swertia-cincta-burkillextract-against-anit-induced-cholestasis-in-rats-by-modulating-the-expression-of-transporters-and-metabolic-enzymes
#19
Lili Xu, Tingting Sheng, Xiaolong Liu, Tong Zhang, Zhengtao Wang, Han Han
ETHNOPHARMACOLOGICAL RELEVANCE: Swertia cincta Burkill was traditionally used for treating jaundice and various types of chronic and acute hepatitis in Yunnan and Tibet in China for hundreds of years. This study aims to investigate the protective effect of S. cincta Burkill (ESC) extract on alpha-naphthylisothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in rats. MATERIALS AND METHODS: Crude extracts were prepared using 90% ethanol and by vacuum drying...
July 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#20
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
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