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Targeting uptake transporters for cancer imaging and treatment

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Acta Pharmaceutica Sinica B 2020年第1期10卷 79-90页

作者： Yuchen Zhang joanne Wang Department of Pharmaceutics University of WashingtonSeattleWA 98195USA

Cancer cells reprogram their gene expression to promote growth,survival,proliferation,and *** unique expression of certain uptake transporters in cancers and their innate function to concentrate small molecular substrates in cells make them ideal targets for selective delivering imaging and therapeutic agents into cancer *** this review,we focus on several solute carrier(SLC)transporters known to be involved in transporting clinically used radiopharmaceutical agents into cancer cells,including the sodium/iodine symporter(NIS),norepinephrine transporter(NeT),glucose transporter 1(GLUT1),and monocarboxylate transporters(MCTs).The molecular and functional characteristics of these transporters are reviewed with special emphasis on their specific expressions in cancers and interaction with imaging or theranostic agents[e.g.,Ⅰ-123,Ⅰ-131,123Ⅰ-iobenguane(mIBG),18F-fluorodeoxyglucose(18F-FDG)and 13C pyruvate].Current clinical applications and research areas of these transporters in cancer diagnosis and treatment are ***,we offer our views on emerging opportunities and challenges in targeting transporters for cancer imaging and *** analyzing the few clinically successful examples,we hope much interest can be garnered in cancer research towards uptake transporters and their potential applications in cancer diagnosis and treatment.

关键词： Uptake transporter Warburg effect Cancer imaging Neuroblastoma Thyroid cancer mIBG

Seasonal Rainfall Forecasts for the Yangtze River Basin of China in Summer 2019 from an Improved Climate Service

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Journal of Meteorological Research 2020年第5期34卷 904-916页

作者： Philip e.BeTT Nicola martin Adam A.SCAIFe Nick DUNSTONe Gill M.martin Nicola GOLDING joanne CAMP Peiqun ZHANG Chris D.HeWITT Leon HeRMANSON Chaofan LI Hong-Li ReN Ying LIU Min LIU Met Office Hadley Centre Exeter EXI 3PBUK Plymouth Marine Laboratory Plymouth PL13DHUK College of engineering Mathematics and Physical SciencesUniversity of ExeterDevon EX44QFUK Laboratory for Climate Studies National Climate CenterChina Meteorological AdministrationBeijing 100081China University of Southern Queensland Toowoomba QLD 4350Australia Center for Monsoon System Research Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Collaborative Innovation Center on Forecast and evaluation of Meteorological Disasters Nanjing University of Information Science&TechnologyNanjing 210044China Wuhan Regional Climate Center Wuhan 430074China

Rainfall forecasts for the summer monsoon season in the Yangtze River basin(YRB) allow decision-makers to plan for possible flooding, which can affect the lives and livelihoods of millions of people. A trial climate service was developed in 2016, producing a prototype seasonal forecast product for use by stakeholders in the region, based on rainfall forecasts directly from a dynamical model. Here, we describe an improved service based on a simple statistical downscaling approach. Through using dynamical forecast of an east Asian summer monsoon(eASM) index, seasonal mean rainfall for the upper and middle/lower reaches of YRB can be forecast separately by use of the statistical downscaling, with significant skills for lead times of up to at least three months. The skill in different sub-basin regions of YRB varies with the target season. The rainfall forecast skill in the middle/lower reaches of YRB is significant in May–June–July(MJJ), and the forecast skill for rainfall in the upper reaches of YRB is significant in June–July–August(JJA). The mean rainfall for the basin as a whole can be skillfully forecast in both MJJ and JJA. The forecasts issued in 2019 gave good guidance for the enhanced rainfall in the MJJ period and the near-average conditions in JJA. Initial feedback from users in the basin suggests that the improved forecasts better meet their needs and will enable more robust decision-making.

关键词： seasonal rainfall forecasts climate service Yangtze River basin(YRB) east Asian summer monsoon(eASM)

evolving landscape and novel treatments in, metastatic castrate-resistant prostate cancer

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Asian Journal of Andrology 2013年第3期15卷 342-349页

作者： Paul J Toren martin e Gleave Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver BC V5Z 1M9 Canada

Treatment options for castrate-resistant prostate cancer （CRPC） have advanced in recent years and significantly improved the Outlook for patients with this aggressive and lethal disease. Further understanding of the biology＇of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor （AR） directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC. New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis, microtubules, chaperones, AR and intracellular kinases, as well as immunotherapy, radiopharmaceuticals and bone-targeted agents. The recent improvement in prognosis for CRPC brings continued optimism for further improvements. Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

关键词： prostate cancer treatment resistance androgen receptor antagonists molecular targets

Biomaterials for spinal cord repair

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Neuroscience Bulletin 2013年第4期29卷 445-459页

作者： Agnes e. Haggerty martin oudega Departments of Bioengineering University of Pittsburgh Departments of the Center for the Neural Basis of Cognition University of Pittsburgh Departments of Physical Medicine and Rehabilitation University of Pittsburgh Departments of Neurobiology University of Pittsburgh

Spinal cord injury （SCI） results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCI is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCI. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCI. A plethora of biomaterials is available and has been tested in various models of SCI. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCI.

关键词： spinal cord injury axon regeneration biodegradable materials extracellular matrix proteins functionalrecovery growth factor guidance injury and repair spinal motor neuron

On ultrahigh temperature crustal metamorphism:Phase equilibria,trace element thermometry,bulk composition,heat sources,timescales and tectonic settings

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Geoscience Frontiers 2015年第3期6卷 311-356页

作者： David e.Kelsey martin Hand Department of Geology and Geophysics School of Physical SciencesThe University of Adelaide

Ultrahigh temperature （UHT） metamorphism is the most thermally extreme form of regional crustal metamorphism, with temperatures exceeding 900 ℃. UHT crustal metamorphism is recognised in more than 50 localities globally in the metamorphic rock record and is accepted as ＇normal＇ in the spectrum of regional crustal processes. UHT metamorphism is Wpically identified on the basis of diagnostic mineral assemblages such as sapphirine ＋ quartz, orthopyroxene ＋ sillimanite ＋ quartz and osumilite in Mg-Al- rich rock compositions, now usually coupled with pseudosection-based thermobarometry using internally-consistent thermodynamic data sets and/or Al-in-Orthopyroxene and ternary feldspar thermobarometry. Significant progress in the understanding of regional UHT metamorphism in recent years includes：（1） development of a ferric iron activity-composition thermodynamic model for sapphirine, allowing phase diagram calculations for oxidised rock compositions; （2） quantification of UHT conditions via trace element thermometry, with Zr-in-rutile more commonly recording higher temperatures than Ti-in-zircon. Rutile is likely to be stable at peak UHT conditions whereas zircon may only grow as UHT rocks are cooling. In addition, the extent to which Zr diffuses out of rutile is controlled by chemical communication with zircon; （3） more fully recognising and utilising temperature-dependent thermal properties of the crust, and the possible range of heat sources causing metamorphism in geodynamic modelling studies; （4） recognising that crust partially melted either in a previous event or earlier in a long-duration event has greater capacity than fertile, unmelted crust to achieve UHT conditions due to the heat energy consumed by partial melting reactions; （5） more strongly linking U-Pb geochronological data from zircon and monazite to P-T points or path segments through using Y ＋ Ree partitioning between accessory and major phases, as well as phase diagrams incorporating Zr and Ree; and （

关键词： Sapphirine + quartz P-T pseudosections Zr-in-rutile Ti-in-zircon U-Pb geochronology Subduction

SARS-CoV-2 spike protein-ACe2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1174-1185页

作者： Sumit Bhattacharyya joanne K.Tobacman Jesse Brown VA Medical Center and University of Illinois at Chicago ChicagoIL 60612USA

Immunostaining in lungs of patients who died with CovID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase(Arylsulfatase B;ARSB).To explain these findings,human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain(SPRBD)and transcriptional mechanisms were ***-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD,and their inhibition suppressed the promoter activation of the carbohydrate sulfotransferases CHST15 and CHST11,which contributed to chondroitin sulfate *** in ARSB was mediated by phospho-38 MAPK-induced N-terminal Rb phosphorylation and an associated increase in Rb-e2F1 binding and decline in e2F1 binding to the ARSB *** increases in chondroitin sulfotransferases were inhibited when treated with phospho-p38-MAPK inhibitors,SMAD3(SIS3)inhibitors,as well as antihistamine desloratadine and antibiotic *** the mouse model of carrageenan-induced systemic inflammation,increases in phosphop38 MAPK and expression of CHST15 and CHST11 and declines in DNA-e2F binding and ARSB expression occurred in the lung,similar to theobserved effects in this SPRBD model of COVID-19 *** accumulation of chondroitin sulfates is associated with fibrotic lung conditions and diffuse alveolar damage,increased attention to p38-MAPK inhibition may be beneficial in amelioratingCovid-19infections.

关键词： ACe2 lung inhibited

Structural and functional reorganization of propriospinal connections promotes functional recovery after spinal cord injury

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Neural Regeneration Research 2015年第4期10卷 509-513页

作者： Linard Filli martin e.Schwab Laboratory for Sensorimotor Function Department of NeurologyUniversity Hospital Zurich Brain Research Institute University of Zurich and Department of Health Sciences and Technology

Axonal regeneration and ifber regrowth is limited in the adult central nervous system, but re-search over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance ifber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of struc-tural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The for-mation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identiifed as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the exis-tence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic inter-ventions （e.g., ifber-growth enhancing interventions, rehabilitation）. This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of pro-priospinal circuits to maximize functional recovery after spinal cord injury.

关键词： spinal cord injury propriospinal system neural plasticity fiber sprouting neural repair compensation regeneration propriospinal detours

Predator-prey distance and latency to flee from an immobile predator： functional relationship and importance

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Current Zoology 2016年第2期62卷 117-122页

作者： William e. COOPeR JR Jose martin Department of Biology Indiana University Purdue University Fort Wayne Fort Wayne IN 46805 USA Departamento de ecologia evolutiva Museo Nacional de Ciencias Naturales CSIC Madrid Spain

When an immobile prey has detected an immobile predator nearby, predation risk is greater when the predator is closer. Consequently, prey flee with shorter latency as standing distance （predator-prey distance when both are still） decreases. Since it was first reported in 2009, this relationship has been confirmed in the few species studied. However, little is known about the functional relationship between standing distance and latency to flee （LF）. We hypothesized that LF increases as standing distance increases at short distances, but reaches a plateau at longer distances where prey can escape reliably if attacked. We simulated immobile predators by moving slowly into positions near striped plateau lizards Sceloporus virgatus, stopping and then remaining immobile, and recording LF from the stopping time. LF increased from shorter to longer standing distances in a decelerating manner. The relationship was concave downward, and LF was indistinguishable among the longer standing distance groups. Latency to flee appears to reach a plateau or approach an asymptotic value as stand- ing distance increases. The effect size of standing distance was large, indicating that S. virgatus sensi- tively adjusts LF to the level of risk associated with standing distance. Relationships between risk assessment and theoretical zones associated with risk, its assessment by prey, and escape decisions are discussed. effect sizes of standing distance were substantial to large in all studies to date, indicating that standing distance is an important predation risk factor when both predator and prey are immobile.

关键词： antipredatory behavior escape behavior latency to flee squamata standing distance.

Mitochondrial dysfunction in Parkinson＇s disease： a possible target for neuroprotection

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Frontiers in Biology 2014年第6期9卷 489-503页

作者： Jacqueline A. GLeAVe Peter D. PeRRI joanne e. NASH Centre for Neurobiology of Stress Department of Biological Sciences University of Toronto Scarborough Toronto Ontario M1C1A4Canada

Mitochondria are dynamic organelles which are required for maintaining cellular homeostasis. Thus, it is not surprising that irregularities in mitochondrial function result in cellular damage and are linked with neurodegenerative diseases, such as Parkinson＇s disease. evidence that mitochondrial dysfunction is key to the pathogenesis of Parkinson＇s disease is founded in studies in post-mortem tissue from patients with Parkinson＇s disease, and also from genetic studies stemming from patients with familial Parkinson＇s disease. Whether triggered by environmental or genetic factors, mitochondrial dysfunction occurs early in the pathogenic process, and is central to Parkinson＇s disease pathology. As such, targeting the mitochondria to slow or halt disease progression is an attractive strategy for disease-modifying agents in Parkinson＇s disease. Indeed, several therapies which target the mitochondria have been investigated as neuroproteetive treatments for Parkinson＇s disease. This review will discuss the evidence supporting mitochondrial dysfunction in Parkinson＇s disease pathology as well as treatment strategies that target the mitochondria.

关键词： Parkinson's disease mitochondria oxidative stress lysosome UPS