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1.
Curr Cancer Drug Targets ; 19(9): 742-755, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30747067

RESUMO

BACKGROUND: The rapid expansion of genome-wide profiling techniques offers the opportunity to utilize various types of information collected in the study of human health and disease. Overexpression of Polo like kinase 1 (PLK1) is associated with esophageal adenocarcinoma (OAC), however biological functions and molecular targets of PLK1 in OAC are still unknown. OBJECTIVES: Here we performed integrative analysis of two "omics" data sources to reveal high-level interactions of PLK1 associated with OAC. METHODS: Initially, quantitative gene expression (RPKM) was measured from transcriptomics data set of four OAC patients. In parallel, alteration in phosphorylation levels was evaluated in the proteomics data set (mass spectrometry) in OAC cell line (PLK1 inhibited). Next, two "omics" data sets were integrated and through comprehensive analysis possible true PLK1 targets that may serve as OAC biomarkers were assembled. RESULTS: Through experimental validation, small ubiquitin-related modifier 1 (SUMO1) and heat shock protein beta-1 (HSPB1) were identified as novel phosphorylation targets of PLK1. Consequently in vivo, in situ and in silico experiments clearly demonstrated the interaction of PLK1 with putative novel targets (SUMO1 and HSPB1). CONCLUSION: Identification of a PLK1 dependent biosignature in OAC with high confidence in two omics levels proven the robustness and efficacy of our integrative approach.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/metabolismo , Proteoma/análise , Proteínas Proto-Oncogênicas/metabolismo , Transcriptoma , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Mapas de Interação de Proteínas , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteína SUMO-1/genética , Proteína SUMO-1/metabolismo , Células Tumorais Cultivadas , Quinase 1 Polo-Like
2.
Prehosp Disaster Med ; 33(2): 220-224, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29560844

RESUMO

Specific Event Identifiers a. Event type: Outdoor music festival. b. Event onset date: December 3, 2016. c. Location of event: Regatta Point, Commonwealth Park. d. Geographical coordinates: Canberra, Australian Capital Territory (ACT), Australia (-35.289002, 149.131957, 600m). e. Dates and times of observation in latitude, longitude, and elevation: December 3, 2016, 11:00-23:00. f. Response type: Event medical support. Abstract Introduction Young adult patrons are vulnerable to risk-taking behavior, including drug taking, at outdoor music festivals. Therefore, the aim of this field report is to discuss the on-site medical response during a music festival, and subsequently highlight observed strategies aimed at minimizing substance abuse harm. METHOD: The observed outdoor music festival was held in Canberra (Australian Capital Territory [ACT], Australia) during the early summer of 2016, with an attendance of 23,008 patrons. First aid and on-site medical treatment data were gained from the relevant treatment area and service. RESULTS: The integrated first aid service provided support to 292 patients. Final analysis consisted of 286 patients' records, with 119 (41.6%) males and 167 (58.4%) females. Results from this report indicated that drug intoxication was an observed event issue, with 15 (5.1%) treated on site and 13 emergency department (ED) presentations, primarily related to trauma or medical conditions requiring further diagnostics. CONCLUSION: This report details an important public health need, which could be met by providing a coordinated approach, including a robust on-site medical service, accepting intrinsic risk-taking behavior. This may include on-site drug-checking, providing reliable information on drug content with associated education. Luther M , Gardiner F , Lenson S , Caldicott D , Harris R , Sabet R , Malloy M , Perkins J . An effective risk minimization strategy applied to an outdoor music festival: a multi-agency approach. Prehosp Disaster Med. 2018;33(2):220-224.


Assuntos
Serviços Médicos de Emergência/organização & administração , Férias e Feriados , Incidentes com Feridos em Massa/prevenção & controle , Música , Território da Capital Australiana , Redução do Dano , Humanos , Colaboração Intersetorial
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