Cancer Research UK

Résumé

Le Cancer Research UK (ou CRUK) est un centre de recherche et une association caritative de lutte contre le cancer britannique. Le Cancer Research UK est la plus grosse association indépendante de lutte contre le cancer au monde, elle a été formée le par la fusion du Cancer Research Campaign et de l’Imperial Cancer Research, son but est de réduire le nombre de décès dû au cancer en finançant et conduisant des recherches dans le domaine de la prévention, du diagnostic et du traitement des cancers. Elle est entièrement financé par le public (dons, donations, legs, vente). Recherche Le Cancer Research UK comprend un institut de recherche fondamentale, le London Research Institute localisés sur deux sites : à Lincoln's Inn Fields au centre de Londres, et à Clare Hall (South Mimms, Hertfordshire) dans la banlieue de Londres mais finance également des équipes de recherches universitaire et hospitalière à travers tout le Royaume-Uni. La Cancer Research UK publie également la r

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Concepts associés (6)

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Cours associés (7)

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Séances de cours associées (11)

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BACKGROUND: Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, and promotes tumour growth and metastasis. In this study, we examine whether (1) pancreatic cancer cells secrete SEMA5A and (2) that secreted SEMA5A modulates certain phenotypes associated with tumour progression, angiogenesis and metastasis through various other molecular factors and signalling proteins. METHODS AND RESULTS: In this study, we show that human pancreatic cancer cell lines secrete the extracellular domain (ECD) of SEMA5A (SEMA5A-ECD) and overexpression of mouse Sema5A-ECD in Panc1 cells (not expressing SEMA5A; Panc1-Sema5-AECD; control cells - Panc1-control) significantly increases their invasion in vitro via enhanced ERK phosphorylation. Interestingly, orthotopic injection of Panc1-Sema5A-ECD cells into athymic nude mice results in a lower primary tumour burden, but enhances the micrometastases to the liver as compared with Panc1-control cells. Furthermore, there is a significant increase in proliferation of endothelial cells treated with conditioned media (CM) from Panc1-Sema5A-ECD cells and a significant increase in microvessel density in Panc1-Sema5A-ECD orthotopic tumours compared with those from Panc1-control cells, suggesting that the increase in liver micrometastases is probably due to increased tumour angiogenesis. In addition, our data demonstrate that this increase in endothelial cell proliferation by Sema5A-ECD is mediated through the angiogenic molecules - interleukin-8 and vascular endothelial growth factor. CONCLUSION: Taken together, these results suggest that a bioactive, secreted form of Sema5A-ECD has an intriguing and potentially important role in its ability to enhance pancreatic tumour invasiveness, angiogenesis and micrometastases. British Journal of Cancer (2012) 107, 501-507. doi: 10.1038/bjc.2012.298 www.bjcancer.com Published online 10 July 2012 (C) 2012 Cancer Research UK

Nature Publishing Group2012

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Splicy: a web-based tool for the prediction of possible alternative splicing events from Affymetrix probeset data

Philipp Bucher

BACKGROUND: The Affymetrix technology is nowadays a well-established method for the analysis of gene expression profiles in cancer research studies. However, changes in gene expression levels are not the only way to link genes and disease. The existence of gene isoforms specifically linked with cancer or apoptosis is increasingly found in literature. Hence it is of great interest to associate the results of a gene expression study with updated evidences on the transcript structure and its possible variants. RESULTS: We present here a web-based software tool, Splicy, whose primary task is to retrieve data on the mapping of Affymetrix probes to single exons of gene transcripts and displaying graphically this information projected on the gene physical structure.Starting from a list of Affymetrix probesets the program produces a series of graphical displays, each relative to a transcript associated with the gene targeted by a given probe. The information on the transcript-by-transcript and exon-by-exon mapping of probe pairs can be retrieved both graphically and in the form of tab-separated files. The mapping of single probes to NCBI RefSeq or EMBL cDNAs is handled by the ISREC mapping tables used in the CleanEx Expression Reference Database Project. We currently maintain these mappings for most popular human and mouse Affymetrix chips, and Splicy can be queried for matches with human and mouse NCBI RefSeq or EMBL cDNAs. CONCLUSION: Splicy generates probeset annotations and images describing the relation between the single probes and intron/exon structure of the target transcript in all its known variants. We think that Splicy will be useful for giving to the researcher a clearer picture of the possible transcript variants linked with a given gene and an additional view on the interpretation of microarray experiment data. Splicy is publicly available and has been realized in the framework of a bioinformatics grant from the Italian Cancer Research Association.

2007

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Splicy: a web-based tool for the prediction of possible alternative splicing events from Affymetrix probeset data

Philipp Bucher

2007

Nature Publishing Group2012