In silico analysis of pathways activation landscape in oral squamous cell carcinoma and oral leukoplakia.

A subset of patients with oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSCC), harbor dysplastic lesions (often visually identified as leukoplakia) prior to cancer diagnosis. Although evidence suggest that leukoplakia represents an initial step in the progression to cancer, signaling networks driving this progression are poorly understood. Here, we applied in silico Pathway Activation Network Decomposition Analysis (iPANDA), a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in OSCC and pre-neoplastic oral lesions. In tumor samples, our analysis detected major conserved mitogenic and survival signaling pathways strongly associated with HNSCC, suggesting that some of the pathways identified by our algorithm, but not yet validated as HNSCC related, may be attractive targets for future research. While pathways activation landscape in the majority of leukoplakias was different from that seen in OSCC, a subset of pre-neoplastic lesions has demonstrated some degree of similarity to the signaling profile seen in tumors, including dysregulation of the cancer-driving pathways related to survival and apoptosis. These results suggest that dysregulation of these signaling networks may be the driving force behind the early stages of OSCC tumorigenesis. While future studies with larger leukoplakia data sets are warranted to further estimate the values of this approach for capturing signaling features that characterize relevant lesions that actually progress to cancers, our platform proposes a promising new approach for detecting cancer-promoting pathways and tailoring the right therapy to prevent tumorigenesis

Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1BCR-ABL-JAK2 Complex

This is a pre-copyedited, author-produced version of an article accepted for publication in JNCI: Journal of the National Cancer Institute following peer review. The version of record Chen, M., et al. (2013). "Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1–BCR-ABL–JAK2 Complex." JNCI: Journal of the National Cancer Institute 105(6): 405-423. is available online at: https://doi.org/10.1093/jnci/djt006This work was funded by the Canadian Cancer Society (grant 700289), in part by the Canadian Institutes of Health Research, the Leukemia & Lymphoma Society of Canada, and the Cancer Research Society (XJ), the Canadian Cancer Society Research Institute (AE, XJ, CE), Cancer Research UK Programme grant C11074/A11008 (TLH), the Glasgow Experimental Cancer Medicine Centre, which is funded by Cancer Research UK and by the Chief Scientist’s Office (Scotland), and Cancer Research UK grant C973/A9894 (JP, JS). M. Chen was supported by a fellowship from Lymphoma Foundation Canada, and P. Gallipoli was supported by Medical Research Council grant G1000288. X. Jiang was a Michael Smith Foundation for Health Research Scholar

Biologie des protéines CD1a, CD1b et CD1c (De l'expression monocytaire à la présentation de l'antigène par les cellules dendritiques)

Les protéines CD1a, CD1b et CD1c sont des molécules non classiques de présentation de l'antigène. Leur structure est analogue à celle des protéines du complexe majeur d'histocompatibilité de classe I. Exprimées par les cellules dendritiques, elles présentent des antigènes lipidiques à des lymphocytes T spécifiques qui vont participer aux réponses immunes anti-infectieuses et anti-tumorales. Après un rappel de l'état des connaissances sur les protéines CD1 du groupe I et les cellules dendritiques, ce manuscrit présente tout d'abord les résultats de trois études s'intéressant à l'expression monocytaire des protéines CD1 dans la drépanocytose et sa relation avec la susceptibilité aux infections bactériennes. Dans un deuxième temps sont développées les études de l'organisation membranaire de la protéine CD1a, son impact sur l'activation lymphocytaire T et l'implication de CD1a dans l'induction d'un signal de maturation de la cellule dendritique.CD1a, CD1b and CD1c proteins are non classical MHC-class I antigen presenting molecules. They display structural homology with MHC-class I proteins. Expressed on dendritic cells, they present glycolipid antigens to specific T lymphocytes with participate to anti-infectious and anti-tumoral immune responses. After an extensive review on CD1 antigen presenting system and dendritic cell populations, this manuscript presents firstly three studies on CD1 expression on monocytes in sickle cell disease and its relation with susceptibility towards severe bacterial infection. In a second part data on CD1a membrane organization and its impact on T cell activation and dendritic cell maturation are presented.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

<i>TET2</i> mutational status affects myelodysplastic syndrome evolution to chronic myelomonocytic leukemia

International audienc