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Keiji Kobashi, Anussara Prayongrat, Takuya Kimoto, Chie Toramatsu, Yasuhiro Dekura, Norio Katoh, Shinichi Shimizu, Yoichi M Ito, Hiroki Shirato
Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix...
March 12, 2018: Journal of Radiation Research
Michael T Milano, Jimm Grimm, Scott G Soltys, Ellen Yorke, Vitali Moiseenko, Wolfgang A Tomé, Arjun Sahgal, Jinyu Xue, Lijun Ma, Timothy D Solberg, John P Kirkpatrick, Louis S Constine, John C Flickinger, Lawrence B Marks, Issam El Naqa
PURPOSE: Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation...
January 31, 2018: International Journal of Radiation Oncology, Biology, Physics
Anussara Prayongrat, Kikuo Umegaki, Arjen van der Schaaf, Albert C Koong, Steven H Lin, Thomas Whitaker, Todd McNutt, Naruhiro Matsufuji, Edward Graves, Masahiko Mizuta, Kazuhiko Ogawa, Hiroyuki Date, Kensuke Moriwaki, Yoichi M Ito, Keiji Kobashi, Yasuhiro Dekura, Shinichi Shimizu, Hiroki Shirato
Particle beam therapy (PBT), including proton and carbon ion therapy, is an emerging innovative treatment for cancer patients. Due to the high cost of and limited access to treatment, meticulous selection of patients who would benefit most from PBT, when compared with standard X-ray therapy (XRT), is necessary. Due to the cost and labor involved in randomized controlled trials, the model-based approach (MBA) is used as an alternative means of establishing scientific evidence in medicine, and it can be improved continuously...
February 24, 2018: Journal of Radiation Research
Katharina Bell, Yvonne Dzierma, Melanie Morlo, Frank Nüsken, Norbert Licht, Christian Rübe
BACKGROUND: In order to consider potential positioning errors there are different recipes for safety-margins for CTV-to-PTV expansion. The aim of this study is to simulate the effect of positioning inaccuracy with clinically realistic patient treatment plans. METHODS: For a collective of 40 prostate patients, the isocenter was shifted back appropriately to the applied table shifts after positioning verification, simulating that no positioning correction had been performed and the treatment plans were recalculated...
February 2018: Physica Medica: PM
Masanori Tachikawa, Yuna Sumiyoshiya, Daisuke Saigusa, Kazunari Sasaki, Michitoshi Watanabe, Yasuo Uchida, Tetsuya Terasaki
The purpose of the present study was to clarify the molecular basis of zonated drug distributions in mouse liver based on the protein expression levels of transporters and metabolizing enzymes in peri-portal vein (PP) and peri-central vein (PC) regions of mouse hepatic lobules. The distributions of sulforhodamine 101 (SR-101), a substrate of organic anion transporting polypeptides (Oatps), and ribavirin, a substrate of equilibrative nucleoside transporter 1 (Ent1), were elucidated in frozen liver sections of mice to which each compound had been intravenously administered...
March 5, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
M Duijm, H Tekatli, E Oomen-de Hoop, W Verbakel, W Schillemans, B J Slotman, S Senan, J J Nuyttens
PURPOSE: To correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model. METHODS AND MATERIALS: Patients with a central lung tumor from 2 centers, who underwent stereotactic or hypofractionated radiotherapy (≤12 fractions), were analyzed. Doses were recalculated to an equivalent dose of 2 Gy with an α/β ratio of 10 (EQD2 10 ). The esophagus was manually delineated and DVH-parameters (Dmax,EQD2 , D1cc,EQD2 , D2cc,EQD2 , D5cc,EQD2 ) were analyzed and used for NTCP modeling based on logistic regression analysis...
February 22, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Yushi Wakisaka, Masashi Yagi, Iori Sumida, Masaaki Takashina, Kazuhiko Ogawa, Masahiko Koizumi
BACKGROUND: The incomplete repair (IR) model expresses the cell repair effect from radiation-induced damage over time, which is given little consideration in actual treatment planning. By incorporating the IR model into the normal tissue complication probability (NTCP), the accuracy and safety of treatment plan evaluations concerning the effect of repair can be improved. This study aims to evaluate the impact of incorporating the IR model into the NTCP by varying time-related factors such as the repair half-time (T1/2 ) and the junction-shift sc3hedule in craniospinal irradiation (CSI)...
February 23, 2018: Radiation Oncology
Lena Thomas, Steffi Kantz, Arthur Hung, Debra Monaco, Florian C Gaertner, Markus Essler, Holger Strunk, Wolfram Laub, Ralph A Bundschuh
PURPOSE: The purpose of our study was to show the feasibility and potential benefits of using68 Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model...
February 21, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Rosario Casillas, David Tabernero, Josep Gregori, Irene Belmonte, Maria Francesca Cortese, Carolina González, Mar Riveiro-Barciela, Rosa Maria López, Josep Quer, Rafael Esteban, Maria Buti, Francisco Rodríguez-Frías
AIM: To determine the variability/conservation of the domain of hepatitis B virus (HBV) preS1 region that interacts with sodium-taurocholate cotransporting polypeptide (hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism (S267F, NTCP variant) in a Spanish population. METHODS: Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection (CHB) ( n = 41, 73% Caucasians), patients with resolved HBV infection ( n = 100, 100% Caucasians) and an HBV-uninfected control group ( n = 105, 100% Caucasians)...
February 14, 2018: World Journal of Gastroenterology: WJG
Jamie E Moscovitz, Amit S Kalgutkar, Kelly Nulick, Nathaniel Johnson, Zhiwu Lin, Theunis C Goosen, Yan Weng
The potential for drug-drug interactions (DDIs) arising from transcriptional regulation of drug disposition genes via activation of nuclear receptors (NRs) such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), and/or aryl hydrocarbon receptor (AhR) remains largely unexplored, as highlighted in a recent guidance document from the European Medicines Agency. The goal of this research was to establish PXR/CAR/AhR-specific drug metabolizing enzyme (DME) and transporter gene expression signatures in sandwich-cultured cryopreserved human hepatocytes using selective activators of PXR (rifampin), CAR (CITCO) and AhR (omeprazole)...
February 12, 2018: Journal of Pharmacology and Experimental Therapeutics
Anna Vildhede, Chuong Nguyen, Brian K Erickson, Ryan C Kunz, Richard Jones, Emi Kimoto, Francis Bourbonais, A David Rodrigues, Manthena V Varma
Targeted protein quantification using liquid chromatography-tandem mass spectrometry with stable isotope labelled standards is recognized as the gold standard of practice for protein quantification. Such assays, however, can only cover a limited number of proteins and developing targeted methods for larger numbers of proteins require substantial investment. Alternatively, large-scale global proteomic experiments along with computational methods such as the "total protein approach" (TPA) have the potential to provide extensive protein quantification...
February 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Yulong Kong, Xiaoguang Gao, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Pengyuan Sun, Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice...
February 7, 2018: European Journal of Pharmacology
Manabu Kaneko, Yushi Futamura, Senko Tsukuda, Yasumitsu Kondoh, Tomomi Sekine, Hiroyuki Hirano, Kento Fukano, Hirofumi Ohashi, Wakana Saso, Ryo Morishita, Satoko Matsunaga, Fumihiro Kawai, Akihide Ryo, Sam-Yong Park, Ryosuke Suzuki, Hideki Aizaki, Naoko Ohtani, Camille Sureau, Takaji Wakita, Hiroyuki Osada, Koichi Watashi
Current anti-hepatitis B virus (HBV) agents including interferons and nucleos(t)ide analogs efficiently suppress HBV infection. However, as it is difficult to eliminate HBV from chronically infected liver, alternative anti-HBV agents targeting a new molecule are urgently needed. In this study, we applied a chemical array to high throughput screening of small molecules that interacted with sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for HBV. From approximately 30,000 compounds, we identified 74 candidates for NTCP interactants, and five out of these were shown to inhibit HBV infection in cell culture...
February 9, 2018: Scientific Reports
Jamie Dean, Kee Wong, Hiram Gay, Liam Welsh, Ann-Britt Jones, Ulricke Schick, Jung Hun Oh, Aditya Apte, Kate Newbold, Shreerang Bhide, Kevin Harrington, Joseph Deasy, Christopher Nutting, Sarah Gulliford
Severe acute dysphagia commonly results from head and neck radiotherapy (RT). A model enabling prediction of severity of acute dysphagia for individual patients could guide clinical decision-making. Statistical associations between RT dose distributions and dysphagia could inform RT planning protocols aiming to reduce the incidence of severe dysphagia. We aimed to establish such a model and associations incorporating spatial dose metrics. Models of severe acute dysphagia were developed using pharyngeal mucosa (PM) RT dose (dose-volume and spatial dose metrics) and clinical data...
January 2018: Clinical and Translational Radiation Oncology
Panayiotis Mavroidis, Kevin A Pearlstein, John Dooley, Jasmine Sun, Srinivas Saripalli, Shiva K Das, Andrew Z Wang, Ronald C Chen
BACKGROUND: To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms. METHODS: Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study...
February 2, 2018: Radiation Oncology
Fan Zhang, Yingting Duan, Lili Xi, Mengmeng Wei, Axi Shi, Yan Zhou, Yuhui Wei, Xinan Wu
Bile acids (BAs), the most important endogenous and signaling molecules regulate the target transporters and enzymes at transcriptional level, participate in a wide variety of processes throughout the entire gastrointestinal tract to orchestrate homeostasis in vivo. BAs and their metabolism and transportation appear to follow the clear circadian rhythms, and they are recently proposed also as the potential chronobiological signals that can affect the molecular clock mechanism. Cholecystectomy are believed to affect the circadian rhythms of BAs and the relevant enterohepatic transporters and enzymes systems and their regulatory signaling pathways, for the reason that the circadian cycle of gallbladder filling and emptying play a pivotal role in controlling the flow of bile into the intestine and the enterohepatic circulation of BAs...
January 30, 2018: Chronobiology International
Xiaoying Liu, Grace L Guo, Bo Kong, David B Hilburn, Susan C Hubchak, Seong Park, Brian LeCuyer, Antony Hsieh, Li Wang, Deyu Fang, Richard M Green
Bile acids are endogenous ligands of the nuclear receptor farnesoid X receptor (FXR), and pharmacologic FXR modulators are under development for the treatment of several liver disorders. The inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the unfolded protein response (UPR) is a protective cellular signaling pathway activated in response to endoplasmic reticulum stress. We investigated the role of FXR signaling in the activation of the hepatic XBP1 pathway. Mice were treated with deoxycholic acid (DCA), cholestyramine, GW4064 or underwent bile duct ligation (BDL) and the hepatic UPR activation was measured...
January 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
James C L Chow, Runqing Jiang
This study evaluated the effects of dose-volume and radiobiological dependence on the calculation grid size in prostate volumetric-modulated arc therapy (VMAT) planning. Ten patients with prostate cancer were selected for this retrospective treatment planning study. Prostate VMAT plans were created for the patients using the 6 MV photon beam produced by a Varian TrueBEAM linac with the calculation grid size equal to 1, 2, 2.5, 3, 4, and 5 mm. Dose-volume histograms (DVHs) of targets and organs at risk were generated for different grid sizes...
January 17, 2018: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
Lili Zhu, Lei Wang, Fei Cao, Peng Liu, Haidong Bao, Yumei Yan, Xin Dong, Dong Wang, Zhongyu Wang, Peng Gong
PURPOSE: To investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). METHODS: Rats received vehicle or CA (20, 50, or 100 mg/kg/d) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. RESULTS: After BDL, plasma levels of ALT, AST, total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology...
January 23, 2018: Journal of Hepato-biliary-pancreatic Sciences
N Patrik Brodin, Rafi Kabarriti, Madhur K Garg, Chandan Guha, Wolfgang A Tomé
There has recently been an increasing interest in model-based evaluation and comparison of different treatment options in radiation oncology studies. This is partly driven by the considerable technical advancements in radiation therapy of the last decade, leaving radiation oncologists with a multitude of options to consider. In lieu of randomized trials comparing all of these different treatment options for varying indications, which is unfeasible, treatment evaluations based on normal tissue complication probability (NTCP) models offer a practical alternative...
February 1, 2018: International Journal of Radiation Oncology, Biology, Physics
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