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Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma

World Journal of Clinical Oncology 2019年第3期10卷 149-160页

作者： Jennifer Wu Merly Contratto Krishna P Shanbhogue Gulam A Manji Bert H O'Neil Anne Noonan robert tudor Ray Lee Division of Hematology and Oncology Perlmutter Cancer CenterNew York University School of Medicine Department of Radiology at New York University School of Medicine Division of Hematology and Oncology Columbia University Medical Center Division of Hematology and Oncology Indiana University Division of Hematology and Oncology Ohio State University Medical Center Roche Pharmaceutical Company Roche and Teclison Pharmaceutical Company

BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in *** To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to *** In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of *** Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased *** study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes

关键词： Hepatocellular carcinoma Hypoxia-inducible factor 1α RO7070179,Superresponder Dynamic contrast-enhanced-magnetic resonance imaging

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The influence of metabolic imbalances and oxidative stress on the outcome of critically ill polytrauma patients: a review

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Burns & Trauma 2017年第1期5卷 17-23页

作者： Alexandru Florin Rogobete Dorel Sandesc Marius Papurica Emil robert Stoicescu Sonia Elena Popovici Lavinia Melania Bratu Corina Vernic Adriana Mariana Sas Adrian tudor Stan Ovidiu Horea Bedreag Faculty of Medicine Victor Babes University of Medicine and PharmacyStr.Eftimie Murgu Nr.2Timisoara300041TimisRomania Clinic of Anaesthesia and Intensive Care Emergency County Hospital“PiusBrinzeu”Bd.Liviu Rebreanu Nr.156Timisoara300736TimisRomania

The critically ill polytrauma patient presents with a series of associated pathophysiologies secondary to the traumatic injuries. The most important include systemic inflammatory response syndrome (SIRS), sepsis, oxidative stress (OS), metabolic disorders, and finally multiple organ dysfunction syndrome (MODS) and death. The poor outcome of these patients is related to the association of the aforementioned pathologies. The nutrition of the critically ill polytrauma patient is a distinct challenge because of the rapid changes in terms of energetic needs associated with hypermetabolism, sepsis, SIRS, and OS. Moreover, it has been proven that inadequate nutrition can prolong the time spent on a mechanical ventilator and the length of stay in an intensive care unit (ICU). A series of mathematical equations can predict the energy expenditure (EE), but they have disadvantages, such as the fact that they cannot predict the EE accurately in the case of patients with hypermetabolism. Indirect calorimetry (IC) is another method used for evaluating and monitoring the energy status of critically ill patients. In this update paper, we present a series of pathophysiological aspects associated with the metabolic disaster affecting the critically ill polytrauma patient. Furthermore, we present different non-invasive monitoring methods that could help the intensive care physician in the adequate management of this type of patient.

关键词： Critically ill Energy expenditure Indirect calorimetry Metabolic disaster Oxidative stress Overfeeding Underfeeding Polytrauma

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DNA Markers for Selection of Late Blight Resistant Potato Breeding Lines

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American Journal of Plant Sciences 2017年第6期8卷 1197-1209页

作者： Shaohua Chen tudor Borza Bohyun Byun robert Coffin Joyce Coffin Rick Peters Gefu Wang-Pruski Department of Plant Food and Environmental Sciences Faculty of Agriculture Dalhousie University Truro Canada Privar Farm Inc. North Wiltshire Canada Agriculture and Agri-Food Canada Charlottetown Research and Development Centre Charlottetown Canada Fujian Agriculture and Forestry University Fuzhou China

Potato late blight, caused by the oomycete Phytophthora infestans, is one of the most devastating diseases in the agricultural sector around the world. Many genes (R genes) conferring resistance to late blight have been identified in various potato species and most of these R genes have been used in potato breeding. The aim of this study was to develop and validate PCR-based assays for the R genes Rpi-blb1, Rpi-blb2, Rpi-blb3 and Rpi-bt1, to distinguish between late blight resistant and late blight susceptible potato progeny in the given breeding background. A total of 100 breeding progeny were screened for the presence of these R genes and tested for resistance against P. infestans mating type A2, genotype US-8 strain, using detached leaf and tuber rot assays. PCR products for the Rpi-blb1 and Rpi-bt1 resistance genes were identified in the resistant progeny but were absent in the susceptible ones;therefore these PCR assays could differentiate between late blight resistant and susceptible plants. Genotypic data from the DNA markers derived from the Rpi-blb1 and Rpi-bt1 genes was found to correlate with the phenotypic data for foliar late blight but not with data for tuber rot. Our results demonstrate that markers derived from these two R genes could be useful for marker-assisted selection (MAS) for foliar late blight resistance in potato breeding programs.

关键词： Late Blight Phytophthora infestans Resistance R genes DNA Markers

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急性卒中影像学研究路径图Ⅱ

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国际脑血管病杂志 2014年第2期22卷 81-92页

作者： Max Wintermark Gregory W. Albers Joseph P. Broderick Andrew M. Demchuk Jochen B. Fiebach Jens Fiehler James C. Grotta Gary Houser tudor G. Jovin Kennedy R. Lees Michael H. Lev David S. Liebeskind Marie Luby Keith W. Muir Mark W. Parsons Rudiger von Kummer Joanna M. Wardlaw Ona Wu Albert J. Yoo Andrei V. Alexandrov Jeffry R. Alger Richard I. Aviv Roland Bammer Jean-Claude Baron Fernando Calamante Bruce C.V. Campbell Trevor C. Carpenter Sφren Christensen William A. Copen Colin P. Derdeyn E. Clarke Haley Jr Pooja Khatri Kohsuke Kudo Maarten G. Lansberg Lawrence L. Latour Ting-Yim Lee Richard Leigh Weili Lin Patrick Lyden Grant Mair Bijoy IC Menon Patrik Michel robert Mikulik Raul G. Nogueira Left φstergaard Salvador Pedraza Christian H. Riedel Howard A. Rowley Pina C. Sanelli Makoto Sasaki Jeffrey L. Saver Pamela W. Schaefer Peter D. Schellinger Georgios Tsivgoulis Lawrence R. Wechsler Philip M. White Greg Zaharchuk Osama O. Zaidat Stephen M. Davis Geoffrey A. Donnan Anthony J. Furlan Werner Hacke Dong-Wha Kang Chelsea Kidw ell Vincent N. Thijs Gotz Thomalla Steven J. Warach 严晓铭刘牧张晶晶柯开富不详南通大学附属医院神经内科 226001

卒中影像学研究组（StrokeImagingResearchGroup，STIR）、美国神经放射学学会和美国神经放射学学会基金会在过去1年多的时间时举办了一系列的工作会议，最后一次会议于2013年3月9日至10日在华盛顿召开的卒中治疗专业学术圆桌会议（Stro... 详细信息

卒中影像学研究组（StrokeImagingResearchGroup，STIR）、美国神经放射学学会和美国神经放射学学会基金会在过去1年多的时间时举办了一系列的工作会议，最后一次会议于2013年3月9日至10日在华盛顿召开的卒中治疗专业学术圆桌会议（Stroke Treatment Academy Industry Roundtable，STAIR）期间举行。

关键词：急性卒中影像学神经放射学路径会议基金会学会美国

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Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID- 19 pandemic

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Stroke & Vascular Neurology 2021年第4期6卷 542-552,I0026-I0032页

作者： Thanh N Nguyen Diogo C Haussen Muhammad M Qureshi Hiroshi Yamagami Toshiyuki Fujinaka Ossama Y Mansour Mohamad Abdalkader Michael Frankel Zhongming Qiu Allan Taylor Pedro Lylyk Omer F Eker Laura Mechtouff Michel Piotin Fabricio Oliveira Lima Francisco Mont'Alverne Wazim Izzath Nobuyuki Sakai Mahmoud Mohammaden Alhamza R Al-Bayati Leonardo Renieri Salvatore Mangiafico David Ozretic Vanessa Chalumeau Saima Ahmad Umair Rashid Syed Irteza Hussain Seby John Emma Griffin John Thornton Jose Antonio Fiorot Rodrigo Rivera Nadia Hammami Anna M Cervantes-Arslanian Hormuzdiyar H Dasenbrock Huynh Le Vu Viet Quy Nguyen Steven Hetts Romain Bourcier Romain Guile Melanie Walker Malveeka Sharma Don Frei Pascal Jabbour Nabeel Herial Fawaz Al-Mufti Atilla Ozcan Ozdemir Ozlem Aykac Dheeraj Gandhi Chandril Chugh Charles Matouk Pascale Lavoie Randall Edgell Andre Beer-Furlan Michael Chen Monika Killer-Oberpfalzer Vitor Mendes Pereira Patrick Nicholson Vikram Huded Nobuyuki Ohara Daisuke Watanabe Dong Hun Shin Pedro SC Magalhaes Raghid Kikano Santiago Ortega-Gutierrez Mudassir Farooqui Amal Abou-Hamden Tatsuo Amano Ryoo Yamamoto Adrienne Weeks Elena A Cora Rotem Sivan-Hoffmann roberto Crosa Markus Möhlenbruch Simon Nagel Hosam Al-Jehani Sunil A Sheth Victor S Lopez Rivera James E Siegler Achmad Fidaus Sani Ajit S Puri Anna Luisa Kuhn Gianmarco Bernava Paolo Machi Daniel G Abud Octavio M Pontes-Neto Ajay K Wakhloo Barbara Voetsch Eytan Raz Shadi Yaghi Brijesh P Mehta Naoto Kimura Mamoru Murakami Jin Soo Lee Ji Man Hong robert Fahed Gregory Walker Eiji Hagashi Steve M Cordina Hong Gee Roh Ken Wong Juan F Arenillas Mario Martinez-Galdamez Jordi Blasco Alejandro Rodriguez Vasquez Luisa Fonseca M Luis Silva Teddy Y Wu Simon John Alex Brehm Marios Psychogios William J Mack Matthew Tenser Tatemi Todaka Miki Fujimura roberta Novakovic Jun Deguchi Yuri Sugiura Hiroshi Tokimura Rakesh Khatri Michael Kelly Lissa Peeling Yuichi Murayama Hugh Stephen Winters Johnny Wong Mohamed Teleb Jeremy Payne Hiroki Fukuda Kosuke Miyake Junsuke Shimbo Yusuke Sug Neurology RadiologyBoston Medical CenterBostonMassachusettsUSA Neurology Marcus Stroke&Neuroscience CenterGrady Memorial HospitalEmory University School of MedicineAtlantaGAUSA Radiology Radiation OncologyBoston University School of MedicineBostonMassachusettsUSA Neurology National Hospital Organization Osaka National HospitalOsakaJapan Neurosurgery National Hospital Organization Osaka National HospitalOsakaJapan Neurology Alexandria UniversityAlexandriaEgypt Radiology Boston Medical CenterBostonMassachusettsUSA Department of Neurology Xinqiao HospitalChongqingChina Neurosurgery University of Cape TownRondeboschWestern CapeSouth Africa Neurosurgery Interventional NeuroradiologyClinica La Sagrada FamiliaBuenos AiresArgentina Neuroradiologie Neurologie VasculaireHospices Civils de LyonLyonAuvergne-Rhône AlpesFrance Neurologie Vasculaire Hospices Civils de LyonLyonAuvergne-Rhône AlpesFrance Interventional Neuroradiology Fondation Ophtalmologique Adolphe de RothschildParisÎle-de FranceFrance Neurology Hospital Geral de FortalezaFortalezaBrazil Interventional Neuroradiology Hospital Geral de FortalezaFortalezaBrazil Neuroradiology Nottingham University Hospitals NHS TrustNottinghamUK Department of Neurosurgery Kobe City Medical Center General HospitalKobeHyogoJapan Interventional Neurovascular Unit University Hospital CareggiFirenzeToscanaItaly Neuroradiology University Hospital Centre ZagrebZagrebCroatia Interventional Neuroradiology Hopital BicetreLe Kremlin-BicetreFrance Stroke and Interventional Neuroradiology Lahore General HospitalLahorePakistan Neurological Institute Cleveland Clinic Abu DhabiAbu DhabiUAE Department of Radiology Beaumont HospitalDublinIreland Neurology Stroke UnitHospital-Estadual CentralVitoriaBrazil Neuroradiology Instituto de Neurocirugia Dr AsengoSantiagoChile Interventional Neuroradiology Institut National de NeurologieTunisTunisia Neurology Boston Medical CenterBostonMassachusettsUSA Neurosurgery Boston Medical Center

Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were *** study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar *** We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke *** with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,*** 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May *** prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal *** There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative *** analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this *** There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 *** findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.

关键词： diagnosis representing subarachnoid

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