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Tumor heterogeneity and therapy resistance-implications for future treatments of prostate cancer

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journal of Cancer Metastasis and Treatment 2017年第1期3卷 302-314页

作者： Fiona M.Frame Amanda R.Noble Sandra Klein Hannah F.Walker Rakesh Suman Richard Kasprowicz Vin M.Mann Matt S.Simms norman j.maitland Cancer Research Unit Department of BiologyUniversity of YorkHeslingtonNorth Yorkshire YO105DDUK Black Family Stem Cell Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Phase Focus Limited Electric WorksSheffield Digital CampusSheffield S12BJUK Department of Urology Castle Hill Hospital(Hull and East Yorkshire Hospitals NHS Trust)Cottingham HU165JQUK Hull York Medical School University of HullHull HU67RXUK.

Aim:To develop new therapies for prostate cancer,disease heterogeneity must be *** includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic *** requires more representative models to be used in more innovative ***:This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient *** assays were used;alamar blue,colony forming assays,γH2AX and Ki67 immunofluorescence and comet *** quantitative phase imaging(QPI),a label-free imaging technique,combined with Cell Analysis Toolbox software,was implemented to carry out real-time analysis of cells and to retrieve morphological,kinetic and population ***:A combination of radiation and Vorinostat may be more effective than radiation *** prostate cancer stem-like cells are more resistant to etoposide than more differentiated *** of QPI images showed that cell lines and primary cells differ in their size,motility and proliferation rate.A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary ***:Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular *** of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.

关键词： Prostate ptychography live-cell imaging primary cells quantitative phase imaging

Expression and regulation of aldehyde dehydrogenases in prostate cancer

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journal of Cancer Metastasis and Treatment 2018年第1期4卷 515-531页

作者： Ali I.M.Ibrahim Maria Sadiq Fiona M.Frame norman j.maitland Klaus Pors Institute of Cancer Therapeutics School of Pharmacy and Medical SciencesFaculty of Life SciencesUniversity of BradfordWest Yorkshire BD71DPUK Department of Pharmacy Al-Zaytoonah University of JordanAmman 11733Jordan Cancer Research Unit Department of BiologyUniversity of YorkHeslingtonNorth Yorkshire YO105DDUK

The functional role of aldehyde dehydrogenases(ALDHs)in prostate cancer remains an area of some *** studies have used high ALDH functional activity to isolate putative cancer stem cells with tumour-initiating and propagating properties,while evidence is also emerging about the involvement of specific isoforms in migration,invasiveness and *** of specific ALDH isoforms,which contribute to both drug resistance and aggressiveness of the disease remains a challenge within the complex heterogeneity of prostate *** purpose of this perspective is to dissect functional roles for ALDH in the tumour microenvironment and to evaluate the potential of the ALDH gene family as biomarkers and/or targets for therapeutic intervention.

关键词： Aldehyde dehydrogenase retinoic acid prostate cancer castration-resistant prostate cancer cancer stem cells multidrug resistance

A fusion at the root of prostate cancer

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Asian journal of Andrology 2013年第5期15卷 592-593页

作者： norman j.maitland YCR Cancer Research Unit Dept of Biology Universityof York York Y010 5DD UK

Many hematopoietic malignancies have oncogenic gene fusions, like BCR-ABL, in their tumor-initiating cells. This implicates the product of the fusion as a powerful cancer-initiating event. In human prostate cancers, d... 详细信息

关键词： A fusion the root prostate cancer

Diet variability of snappers(Teleostei:Lutjanidae)in a bay-to-reef ecosystem of the Mexican Caribbean

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Water Biology and Security 2024年第1期3卷 53-59页

作者： Leon Felipe Martínez-juarez juan j.Schmitter-Soto Nancy Cabanillas-Teran norman Mercado-Silva El Colegio de la Frontera Sur 77014ChetumalQuintana RooMexico Centro de Investigacion en Biodiversidad y Conservacion Universidad Autonoma del Estado de Morelos62209CuernavacaMorelosMexico

Fishes use environmental resources *** ontogenic movements among coastal habitats lead to diverse *** investigated the diets of seven snapper species(Lutjanus apodus,***,***,***,***,***,and Ocyurus chrysurus)in three interconnected coastal environments in the western Caribbean:Río Huach channel,Chetumal/Corozal bay,and the adjacent Xcalak reef *** three encompass all habitats used by the seven species in the study *** diets were mostly composed of fish and crustaceans,but dominance of either group varied among the studied habitats;for example,fish were the main prey for *** from the reef lagoon zone,but second in the *** are piscivorous-invertivorous mesopredators;the species that relied the most on fishes were *** and ***,whereas *** preferred *** content results revealed a high degree of dietary overlap among *** findings suggested a tradeoff in relative weight between fish and crustaceans as the main food source of snappers at these connected areas,supporting the hypothesis of niche *** results can be used as a baseline to further our understanding of the ecology and differences in resource use by snapper species in an area undergoing important anthropogenic changes.

关键词： Resource partitioning Chetumal/Corozal bay Quintana Roo Trophic ecology

Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

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World journal of Gastrointestinal Surgery 2024年第3期16卷 740-750页

作者： Phillip Gu Shishir Dube norman Gellada So Yung Choi Susan Win Yoo jin Lee Shaohong Yang Talin Haritunians Gil Y Melmed Eric A Vasiliauskas Niru Bonthala Gaurav Syal Andres j Yarur David Ziring Shervin Rabizadeh Phillip Fleshner Cindy Kallman Suzanne Devkota Stephan R Targan Dalin Li Dermot PB McGovern Department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Imaging Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Biostatistics Shared Resource Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Internal Medicine Keimyung University School of MedicineDaegu 42601South Korea Department of Medicine University of California at Los AngelesLos AngelesCA 90095United States Department of Medicine University of California at San DiegoSan DiegoCA 92093United States Department of Pediatrics Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory ***,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional *** advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential ***,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after *** strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off ***,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee Yj and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting

关键词： Crohn’s disease Surgery Visceral adipose tissue Mesenteric adipose tissue Creeping fat Computed tomography

Inelastic Cotunneling Current and Shot Noise of an Interacting Quantum Dot with Ferromagnetic Correlations

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Communications in Theoretical Physics 2007年第12期48卷 1099-1106页

作者： norman j.M.Horing Department of Physics and Engineering Physics Stevens Institute of TechnologyHobokenNew Jersey 07030USA

We explore inelastic cotunneling through a strongly Coulomb-blockaded quantum dot attached to twoferromagnetic leads in the weak coupling limit using a generic quantum Langevin equation *** first developa B1och-type equation microscopically to describe the cotunneling-induced spin relaxation dynamics,and then developexplicit analytical expressions for the local magnetization,current,and its *** this basis,we predict a novelzero-bias anomaly of the differential conductance in the absence of a magnetic field for the anti-parallel configuration,and asymmetric peak splitting in a magnetic ***,for the same system with large polarization,we find a negativezero-frequency differential shot noise in the low positive bias-voltage region. All these effects are ascribed to rapidspin-reversal due to underlying spin-flip cotunneling.

关键词： quantum dot spin polarized tunneling cotunneling

Transitioning from paternalism to empowerment of farmers in lowincome countries: Farming components to systems

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journal of Integrative Agriculture 2015年第8期14卷 1490-1499页

作者： David norman Agricultural Economics Department Kansas State University

Reasons for the initiation of farming systems/participatory approaches in non-Green Revolution（i.e., in more heterogeneous and less favourable production environments） areas in low-income countries is followed by a discussion of their *** phases are described along, with a brief description of some of the significant methods in which farmer participation has been sought, accessed and *** enabled/facilitated the evolutionary ***, over the last 40 years there has been a progress in making small-scale farmers much more visible in driving the agricultural research/development agenda through using the four basic stages embodied in the farming systems approach（i.e., descriptive, diagnosis, testing/evaluation and finally dissemination）, much still needs to be *** leads on to a discussion as to some of the barriers still inhibiting true farmer empowerment and why further, such empowerment is imperative, if the agricultural challenges of this century are to be addressed successfully, namely substantially increasing agricultural productivity in an ecologically sustainable *** the heterogeneity of the production environments and that many identified improvements are likely to be incremental rather than revolutionary in nature, this will require farmers＇ intimate involvement in their identification, evaluation and *** in the paper recognizes that there is increasing globalization/commercialization of agriculture and is predicated on the need to consider the whole farmer-research-development continuum involving multiple stakeholders（i.e., farmers, scientists, extension workers, input/output service providers and policymakers）.Such a continuum has been explicitly recognized in the operational plans for the recently reformed international agricultural research（i.e., CGIAR） *** paper concludes with a short discussion on the potential role of formal modelling.

关键词： farming systems research farmer empowerment farmer participatory approaches/techniques globalisation commercialisation conservat

Transferring Western Management Knowledge to China： Perceptions of Graduates from an American Executive MBA Program

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Frontiers of Business Research in China 2013年第1期7卷 82-105页

作者： Mahmood A. Zaidi Thomas j. norman Carlson School of Management University of Minnesota Minneapolis MN 55455 USA College of Business Administration and Public Policy California State University--Dominguez Hills Carson CA 90747 USA

As is well-known, China＇s rapid economic growth over the past decades has been impressive and this growth has driven the demand of qualified managers and professionals by both foreign and Chinese enterprises. This paper examines perceptions of the graduates of an American Executive MBA program, who experienced the transfer of Western management knowledge through team teaching and virtual student teams. The findings show that graduates are generally satisfied with their overall educational experience and its impact on their career in terms of promotions and compensation. Furthermore, the team teaching and global virtual student teams are viewed as valuable experiences.

关键词： EMBA graduate perceptions team teaching virtual internationalstudents teams

Current landscape in motoneuron regeneration and reconstruction for motor cranial nerve injuries

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Neural Regeneration Research 2020年第9期15卷 1639-1649页

作者： Yanjun Xie Kevin j.Schneider Syed A.Ali norman D.Hogikyan Eva L.Feldman Michael j.Brenner Department of Otolaryngology-Head and Neck Surgery University of Michigan Medical SchoolAnn ArborMIUSA Department of Neurology University of Michigan Medical SchoolAnn ArborMIUSA

The intricate anatomy and physiology of cranial nerves have inspired clinicians and scientists to study their roles in the nervous system. Damage to motor cranial nerves may result from a variety of organic or iatrogenic insults and causes devastating functional impairment and disfigurement. Surgical innovations directed towards restoring function to injured motor cranial nerves and their associated organs have evolved to include nerve repair, grafting, substitution, and muscle transposition. In parallel with this progress, research on tissue-engineered constructs, development of bioelectrical interfaces, and modulation of the regenerative milieu through cellular, immunomodulatory, or neurotrophic mechanisms has proliferated to enhance the available repertoire of clinically applicable reconstructive options. Despite these advances, patients continue to suffer from functional limitations relating to inadequate cranial nerve regeneration, aberrant reinnervation, or incomplete recovery of neuromuscular function. These shortfalls have profound quality of life ramifications and provide an impetus to further elucidate mechanisms underlying cranial nerve denervation and to improve repair. In this review, we summarize the literature on reconstruction and regeneration of motor cranial nerves following various injury patterns. We focus on seven cranial nerves with predominantly efferent functions and highlight shared patterns of injuries and clinical manifestations. We also present an overview of the existing reconstructive approaches, from facial reanimation, laryngeal reinnervation, to variations of interposition nerve grafts for reconstruction. We discuss ongoing endeavors to promote nerve regeneration and to suppress aberrant reinnervation and the development of synkinesis. Insights from these studies will shed light on recent progress and new horizons in understanding the biomechanics of peripheral nerve neurobiology, with emphasis on promising strategies for optimizing

关键词： axon degeneration cranial neuropathy facial nerve facial paralysis motoneuron nerve regeneration peripheral nerve recurrent laryngeal nerve synkinesis vocal fold paralysis