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1.
Int J Cancer ; 146(10): 2845-2854, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32037533

RESUMO

Transcriptomic profiling of metastatic cancer can illuminate mechanisms of progression and lead to new therapies, but standard biopsy is invasive and reflects only a single metastatic site. In contrast, circulating tumor cell (CTC) profiling is noninvasive and repeatable, reflecting the dynamic and systemic nature of advanced disease. To date, transcriptomic profiling of CTCs has not delivered on its full potential, because white blood cells (WBCs) vastly outnumber CTCs. Current profiling strategies either lack cancer sensitivity and specificity or require specialized CTC capture protocols that are not readily scalable to large patient cohorts. Here, we describe a new strategy for rapid CTC enrichment and transcriptomic profiling using commercially available WBC depletion, microfluidic enrichment and RNA sequencing. When applied to blood samples from patients with advanced prostate cancer (PC), transcriptomes from enriched samples cluster with cancer positive controls and previously undetectable prostate-specific transcripts become readily measurable. Gene set enrichment analysis reveals multiple significantly enriched signaling pathways associated with PC, as well as novel pathways that merit further study. This accessible and scalable approach yields cancer-specific transcriptomic data and can be applied repeatedly and noninvasively in large cancer patient cohorts to discover new therapeutic targets in advanced disease.


Assuntos
Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Células Neoplásicas Circulantes , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Humanos , Masculino
2.
Cytometry A ; 93(12): 1234-1239, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30107082

RESUMO

Cancer cells from solid tumors can enter the circulatory system and survive to subsequently form distant metastases. The CellSearch® system (Menarini-Silicon Biosystems, Huntingdon Valley, PA) was the first, FDA-cleared system that provided a reliable tool for the investigation of circulating tumor cells (CTCs), which have been shown to be strongly associated with poor survival and therapy failure. Since that time, a number of new technologies have been introduced to improve CTC detection and/or isolation for further characterization. The continued and growing interest in the "liquid biopsy" field has spurred the development of numerous different CTC technologies. However, selecting the most appropriate CTC platform for individual applications can be challenging. No consensus has yet been reached in the community regarding which liquid biopsy technology is optimal. Here, we introduce the Parsortix™ Cell Separation System (ANGLE North America, Inc., King of Prussia, PA), a microfluidic based technology that captures rare cells based on size and deformability, offers reproducibly high capture efficiency, and produces highly enriched, viable (viability dependent on preservative used) CTCs that are amenable to a multitude of downstream analyses, including the isolation and interrogation of single cells. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.


Assuntos
Separação Celular/métodos , Biópsia Líquida/métodos , Contagem de Células/métodos , Linhagem Celular Tumoral , Tamanho Celular , Humanos , Células MCF-7 , Microfluídica/métodos , Células Neoplásicas Circulantes/patologia
3.
Perspect Med Educ ; 4(4): 188-190, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26183250

RESUMO

INTRODUCTION: Professionalism is a key attribute for health professionals. Yet, it is unknown how much faculty development is directed toward skills and behaviours of faculty professionalism. Faculty professionalism includes boundaries in teacher-student relationships, self-reflection, assuring one's own fitness for duty, and maintaining confidentiality when appropriate. METHODS: For five years, we have incorporated faculty professionalism as a routine agenda item for the monthly Physician Assistant Programme faculty meetings, allowing faculty members to introduce issues they are comfortable sharing or have questions about. We also have case discussions of faculty professionalism within faculty meetings every three months. RESULTS: Faculty professionalism is important in the daily work lives of faculty members and including this as part of routine agendas verifies its importance. A faculty survey showed that a majority look forward to the quarterly faculty professionalism case discussions. These have included attempted influence in the admissions process, student/faculty social boundaries, civic professionalism, students requesting medical advice, and self-disclosure. CONCLUSION: A preventive approach works better than a reactionary approach to faculty missteps in professionalism. Routine discussion of faculty professionalism normalizes the topic and is helpful to both new and experienced faculty members. We recommend incorporation of faculty professionalism as a regular agenda item in faculty meetings.

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