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Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer,therapeutic treatment options for platinum-resistant ovarian cancer

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Cancer Drug Resistance 2021年第3期4卷 573-595页

作者： natasha Rinne Elizabeth LChristie Anastasia Ardasheva Chun Hei Kwok Nikita Demchenko Caroline Low Catherine Tralau-Stewart Christina Fotopoulou Paula Cunnea Department of Surgery&Cancer Imperial College LondonHammersmith campusLondon W120NNUK Peter MacCallum Cancer Centre East MelbourneVictoria 3002Australia Department of Metabolism Digestion&Reproduction Imperial College LondonLondon W120NNUK Takeda Academic Innovation Center for External InnovationTakeda CaliforniaSan DiegoCA 92121USA

The survival rates for women with ovarian cancer have shown scant improvement in recent years,with a 5-year survival rate of less than 40%for women diagnosed with advanced ovarian ***-grade serous ovarian cancer(HGSOC)is the most lethal subtype where the majority of women develop recurrent disease and chemotherapy resistance,despite over 70%-80%of patients initially responding to platinum-based *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signaling pathway regulates many vital processes such as cell growth,survival and ***,this pathway is frequently dysregulated in cancers including different subtypes of ovarian cancer,through amplification or somatic mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),amplification of AKT isoforms,or deletion or inactivation of *** evidence indicates a role for the PI3K/AKT/mTOR pathway in the development of chemotherapy resistance in ovarian ***,targeting key nodes of the PI3K/AKT/mTOR pathway is a potential therapeutic *** this review,we outline dysregulation of PI3K signaling in ovarian cancer,with a particular emphasis on HGSOC and platinum-resistant *** review pre-clinical evidence for inhibitors of the main components of the PI3K pathway and highlight past,current and upcoming trials in ovarian cancers for different inhibitors of the *** no inhibitors of the PI3K/AKT/mTOR pathway have thus far advanced to the clinic for the treatment of ovarian cancer,several promising compounds which have the potential to restore platinum sensitivity and improve clinical outcomes for patients are under evaluation and in various phases of clinical trials.

关键词： Ovarian cancer high-grade serous PI3K/AKT/mTOR pathway chemotherapy resistance inhibitors therapeutics

Mapping Landscape Positions and Relevance of Two Dambo-Springs in Incalaue River Basin in Niassa Special Reserve,Mozambique:Information for Drought Water Shortage Effects Management

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Journal of Environmental Science and Engineering(B) 2021年第6期10卷 211-226页

作者： Ezrah Natumanya natasha Ribeiro Majaliwa Jackson Gilbert Mwanjalolo Franziska Steinbruch Faculdade de Agronomia e Engenharia Florestal Universidade Eduardo MondlaneAvenida Julius Nyerere 3453Maputo Mozambique College of Agricultural and Environmental Sciences Makerere UniversityP.O.Box 7062KampalaUganda National Administration for Conservation Areas National Administration for Conservation AreasAvenida 10 de Novembronº40Praceta 1196Maputo Mozambiquenº40Praceta 1196Maputo Mozambique

Mapping of topography and land use/cover as well as spring water yield measurements were done for 2 dambo-spring fed micro-catchments in Incalaue river *** springs are located near Ntimbo 1 and Lizongole human settlement areas in Niassa Special Reserve(NSR).Community consultations were used to asses locally perceived knowledge of dambo-spring catchments dependence by these communities and wildlife;as well as changes and *** Ntimbo 1 dambo-spring catchment(26.55 ***)has elevation gradient of 310 to 530 m a.s.l;and the area can topographically be linked to Incalaue river by delineation from a 90-meter spatial resolution Digital Elevation Model(DEM).The Lizongole dambo-spring catchment(1.33 ***)has elevation gradient of 300 to 360 m a.s.l and cannot easily be delineated from 90-meter *** catchments have the 6 vegetation classes existing in the area as well as farmlands and human settlement *** exists potential for wildlife-human water source conflict due to dambo dependence by humans and wildlife in the dry *** dambo-spring had a higher water yield per second than the Lizongole *** was no significant difference in spring yields of Ntimbo and Lizongole in the dry season(P<0.05).The Lizongole spring could not be gauged in the wet season because of the wet dambo valley wetland *** was no significant reduction in water yield for Ntimbo spring during the dry season(P<0.05).The study suggests that Ntimbo spring could be from a confined aquifer;and Lizongole spring to be from a shallow unconfined *** study contributes understanding of the poorly-defined dambo areas by adding the role of groundwater in supporting micro-dambos which support herbaceous flora and graminivorous fauna as well as human populations in Incalaue basin in NSR especially in the dry season.

关键词： Dambos mapping wildlife source springs

Secreted frizzled related-protein 2(Sfrp2)deficiency decreases adult skeletal stem cell function in mice

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Bone Research 2021年第4期9卷 606-617页

作者： Luis Fernandez de Castro Brian丄Sworder Byron Mui Kathryn Futrega Agnes Berendsen Matthew D.Phillips Nathan J.Burbach natasha Cherman Sergei Kuznetsov Yankel Gabet Kenn Holmbeck Pamela G.Robey Skeletal Biology Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthDepartment of Health and Human ServicesNational Institutes of HealthBethesdaMDUSA Department of Molecular Medicine Boston UniversityBostonMAUSA School of Dentistry University of Minnesota-Twin CitiesMinneapolisMNUSA Department of Anatomy and Anthropology Sackler Faculty of MedicineTel Aviv UniversityTel Aviv-YafoIsrael

In a previous transcriptomic study of human bone marrow stromal cells(BMSCs,also known as bone marrow-derived^mesenchymal stem cells#,)/SFRP2 was highly over-represented in a subset of multipotent BMSCs(skeletal stem cells,SSCs),which recreate a bone/marrow organ in an in vivo ectopic bone formation *** modulate WNT signaling,which is essential to maintain skeletal homeostasis,but the specific role of SFRP2 in BMSCs/SSCs is ***,we evaluated Sfrp2 deficiency on BMSC/SSC function in models of skeletal organogenesis and *** skeleton of Sfrp2-def\c\ent(KO)mice is overtly normal;but their BMSCs/SSCs exhibit reduced colony-forming efficiency,reflecting low SSC self-renewal/***2 KO BMSCs/SSCs formed less trabecular bone than those from WT littermates in the ectopic bone formation ***,regeneration of a cortical drilled hole defect was dramatically impaired in Sfrp2 KO ***2-deficient BMSCs/SSCs exhibited poor in vitro osteogenic differentiation as measured by Runx2 and Osterix expression and calcium ***,activation of the Wnt co-receptor;Lrp6,and expression of Wnt target genes,Axin2,C-myc and Cyclin Dl,were reduced in Sfrp2-deficient BMSCs/*** of recombinant Sfrp2 restored most of these activities,suggesting that Sfrp2 acts as a Wnt *** demonstrate that Sfrp2 plays a role in self-renewal of SSCs and in the recruitment and differentiation of adult SSCs during bone ***2 is also a useful marker of BMSC/SSC multipotency,and a factor to potentially improve the quality of ex vivo expanded BMSC/SSC products.

关键词： skeletal impaired healing

Proposing Land Use/Cover Conservation Basing on Connectivity,Changes and Drivers over 20 Years in Incalaue River Basin,Niassa National Reserve in Mozambique

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Journal of Environmental Science and Engineering(A) 2022年第1期11卷 13-27,I0003,28-34页

作者： Natumanya Ezrah natasha Ribeiro Majaliwa Jackson Gilbert Mwanjalolo Franziska Steinbruch Faculdade de Agronomia e Engenharia Florestal Universidade Eduardo Mondlane3453 Avenida Julius NyerereMaputo Mozambique College of Agricultural and Environmental Sciences Makerere UniversityP.O Box 7062 KampalaUganda National Administration for Conservation Areas National Administration for Conservation AreasAvenida 10 de Novembronº40Praceta 1196MaputoMozambiquenº40Praceta 1196MaputoMozambique

Landscape heterogeneity in biodiversity conservation areas can be represented by the size of the geographic range of vegetation cover types and their species composition;and is reflected in historical and contemporary LULC(Land Use/Cover).This study assesses LULC changes in a predominantly vegetated Incalaue river basin in NSR(Niassa Special Reserve)for the years 2001,2009 and 2019 to recommend conservation *** was mapped using the best available Landsat imagery of the area which were L7 EMT+(Landsat 7 Enhanced Thematic Mapper),L5 TM(Landsat 5 Thematic Mapper)and L8 OLI(Landsat 8 Operational Land Imagery).Image classification and remote sensing analysis were done using images of 30-meter resolution using the maximum likelihood supervised classification on ArcGIS ArcMap *** showed that there were gains in area coverfor taller vegetation classes with the major ones being MDW(Medium Density Woodland)which increased by 51.07%;MFS(Mountain Forests)by 36.41%;and HDW(High-Density Woodland)by 17.95%over the studied ***(Normalized Difference Vegetation Index)maps show 2019 with wetter vegetation than 2001;and both wetter than *** spatially dominant vegetation-class was MDW(Medium Density Woodland)covering 27.29%of the basin area largely in the elevation band 410-430 m *** classes do not necessarily follow landform with rocky upstream section(440-510 m a.s.l)having MFS which also existed in lower altitude areas(370-430 m a.s.l);and woodland being randomly distributed across the basin while there was also WET(Wetland)in both upstream and *** are multiple vegetation species localized in distribution in the landscape which makes these to be hotspot areas for *** people in the human settlement areas of Ntimbo 1 and Lizongole recognize vulnerability of ecosystems,environmental change as well as human land use/cover and climate change as the main *** was a large increase in human settlement area(104

关键词： Hydrology landscape vegetation woodland

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国际石油价格的波动对俄罗斯经济的主要影响

国际石油价格的波动对俄罗斯经济的主要影响

作者：娜达莎（natasha）哈尔滨工业大学

学位级别：硕士

俄罗斯石油工业是国家的重要支柱产业，在国民经济发展中具有重要的战略地位，它的逐渐发展扩大也是保障俄罗斯社会安定的必要条件之一。近年来，由于国际油价上涨，所以确保了俄罗斯经济连续多年的快速增长，但是高油价在一定程度上对... 详细信息

俄罗斯石油工业是国家的重要支柱产业，在国民经济发展中具有重要的战略地位，它的逐渐发展扩大也是保障俄罗斯社会安定的必要条件之一。近年来，由于国际油价上涨，所以确保了俄罗斯经济连续多年的快速增长，但是高油价在一定程度上对俄罗斯经济的发展造成了负面的影响，这主要表现在俄罗斯产业结构的变化，以及国家的经济安全和经济稳定方面。本文在对国内外研究现状进行分析之后，重点研究了国际石油价格的波动对俄罗斯微观经济的影响，即包括国际石油价格的波动对工业企业的影响、农业企业影响、居民个人的影响和对国际贸易的影响;国际石油价格的波动对俄罗斯宏观经济的影响，即包括国际石油价格的波动对俄罗斯发展战略，对俄罗斯经济增长的影响以及对俄罗斯经济趋势的影响，并指出了由于国际石油价格的波动使俄罗斯经济发展中所面临亟待解决的问题。根据国际石油价格的波动对俄罗斯微观经济和宏观经济的影响，本文提出了应对石油价格波动的措施，即稳定金融秩序、进行研究对立法及法律监管、修改关税制及完善进出口制度等。本文的新意是利用比较分析等手段，通过国际石油价格的动态变化对俄罗斯经济进行分析，找出对俄罗斯经济积极和负面的影响及存在的一些问题，并提出应对石油价格波动的措施。

关键词：石油工业国际油价经济发展

Five Years, the First Milestone on the ＇Silk Road＇

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Molecular Plant 2013年第1期6卷 1-1页

作者： Sheng Luan Xiao-Ya Chen natasha Raikhel Winslow Briggs Editors Molecular Plant

When Molecular Plant proposed to publish its first issue five years ago, many in the plant biology community questioned the need for another journal. Indeed, establishing a new journal in the field of almost 200 existing international titles proves to be a difficult task. However, colleagues around the world were soon impressed with the quality and rapid turnaround in this new journal. The most exciting and suc- cessful feature of the Journal was its special issues on cur- rent topics in molecular plant sciences that were organized by leading researchers in a particular field.

关键词： The silk road Plant molecular The mileage Biological communities Science organization The researchers

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基因疗法全球研发进展

药学进展 2017年第5期41卷 392-397页

作者： BOLITER natasha Informa Pharma Intelligence

基因疗法能将基因导入细胞内,用于治疗和预防疾病,被称为医学史上的一大革命。近年来,基因治疗在科研领域取得很多重要进展,多个基因疗法药物已进入临床硏究阶段或已上市,为癌症、罕见病、神经性疾病、心血管疾病等多个领域的疾病治疗... 详细信息

基因疗法能将基因导入细胞内,用于治疗和预防疾病,被称为医学史上的一大革命。近年来,基因治疗在科研领域取得很多重要进展,多个基因疗法药物已进入临床硏究阶段或已上市,为癌症、罕见病、神经性疾病、心血管疾病等多个领域的疾病治疗带来新希望。概述并解析基因疗法药物的全球研发进展,包括总体研发态势、作用靶点、适应证、研发阶段、开发公司及产品管线或临床研究情况等。

关键词：基因疗法上市药物癌症罕见病

Development of a chromatographic lateral flow immunoassay for detection of African swine fever virus antigen in blood

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Animal Diseases 2022年第3期2卷 139-153页

作者： Daniel W.Madden Sun-Young Sunwoo natasha N.Gaudreault Jessie D.Trujillo Igor Morozov Carmina Gallardo Juergen A.Richt Department of Diagnostic Medicine/Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKSUSA Centro de Investigación en Sanidad Animal(CISA-INIA/CSIC) MadridSpain

African swine fever(ASF)is a highly lethal disease of domestic and wild swine caused by African swine fever virus(ASFV).The disease currently circulates in Africa,Europe,Asia and on the island of *** ongoing epizootics in Europe and Asia have produced millions of animal deaths and severe economic *** effective vaccine is available for ASF,making rapid and accurate detection of ASFV essential for disease mitigation *** available diagnostics for ASFV possess significant limitations related to assay performance,deployability,and/or turn-around time;therefore there is an unmet need for pen-side diagnostic tests with sufficient sensitivity and specificity.A chromatographic lateral flow immunoassay(LFIA)was developed for the detection of ASFV antigen in EDTA-treated whole blood using monoclonal antibodies targeting the viral p30 *** assay requires only water to perform and provides results in 25 min,making it well-suited for field *** LFIA was capable of detecting genotype I and genotype II strains of ASFV in EDTA blood from experimentally infected pigs at varying time-points after infection,though it was unable to detect a genotype X ASFV *** sensitivity correlated with clinical disease severity,body temperature,and viral DNA levels,and was over 90%in animals showing moderate to severe ASF-related symptoms after challenge with virulent genotype II *** LFIA also showed a robust diagnostic specificity of over 98%,which is essential to field testing for a high consequence to foregin animal *** LFIA targeting the viral p30 protein can reliably detect ASFV in whole blood from animals showing moderate to severe clinical signs of infection with virulent genotype I and II isolates,making it a promising candidate for use as a field-deployable antigen detection *** evaluation using field samples and different virus strains is required to further assess the utility of this rapid diagnostic test.

关键词： African swine fever Lateral flow immunoassay Point of care diagnostics

The response to vedolizumab in chronic granulomatous disease-related inflammatory bowel disease

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Gastroenterology Report 2020年第5期8卷 404-406,I0003页

作者： natasha Kamal Beatriz Marciano Bryan Curtin Anna Strongin Suk See DeRavin Athos Bousvaros Christopher Koh Harry L.Malech Steven M.Holland Christa Zerbe Theo Heller Digestive Disease Branch National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMDUSA Laboratory of Host Defenses National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMDUSA Division of Gastroenterology Hepatology and NutritionBoston Children’s HospitalBostonMAUSA Liver Disease Branch National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMDUSA Laboratory of Clinical Immunology and Microbiology National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMDUSA

Introduction Chronic granulomatous disease(CGD)is a rare immunodeficiency affecting approximately 1 in 200,000 people[1].Patients with CGD are unable to produce normal amounts of neutrophil superoxide and other phagocyte reactive oxygen *** a result,phagocytes have decreased microbicidal activity and patients develop recurrent bacterial and fungal infections.

关键词：慢性肉芽肿单抗治疗炎症性肠病 immunodeficiency