132 research outputs found
Statistical data mining for symbol associations in genomic databases
A methodology is proposed to automatically detect significant symbol
associations in genomic databases. A new statistical test is proposed to assess
the significance of a group of symbols when found in several genesets of a
given database. Applied to symbol pairs, the thresholded p-values of the test
define a graph structure on the set of symbols. The cliques of that graph are
significant symbol associations, linked to a set of genesets where they can be
found. The method can be applied to any database, and is illustrated MSigDB C2
database. Many of the symbol associations detected in C2 or in non-specific
selections did correspond to already known interactions. On more specific
selections of C2, many previously unkown symbol associations have been
detected. These associations unveal new candidates for gene or protein
interactions, needing further investigation for biological evidence
Large scale statistical analysis of GEO datasets
The problem addressed here is that of simultaneous treatment of several gene
expression datasets, possibly collected under different experimental conditions
and/or platforms. Using robust statistics, a large scale statistical analysis
has been conducted over datasets downloaded from the Gene Expression
Omnibus repository. The differences between datasets are compared to the
variability inside a given dataset. Evidence that meaningful biological
information can be extracted by merging different sources is provided
Simultaneous growth of two cancer cell lines evidences variability in growth rates
Cancer cells co-cultured in vitro reveal unexpected differential growth rates
that classical exponential growth models cannot account for. Two
non-interacting cell lines were grown in the same culture, and counts of each
species were recorded at periodic times. The relative growth of population
ratios was found to depend on the initial proportion, in contradiction with the
traditional exponential growth model. The proposed explanation is the
variability of growth rates for clones inside the same cell line. This leads to
a log-quadratic growth model that provides both a theoretical explanation to
the phenomenon that was observed, and a better fit to our growth data
Simulation of Gene Regulatory Networks
This limited review is intended as an introduction to the fast growing subject of mathematical modelling of cell metabolism and its biochemical pathways, and more precisely on pathways linked to apoptosis of cancerous cells. Some basic mathematical models of chemical kinetics, with emphasis on stochastic models, are presented
The Pro-tumorigenic IL-33 Involved in Antitumor Immunity: A Yin and Yang Cytokine
Interleukin-33 (IL-33), considered as an alarmin released upon tissue stress or damage, is a member of the IL-1 family and binds the ST2 receptor. First described as a potent initiator of type 2 immune responses through the activation of T helper 2 (TH2) cells and mast cells, IL-33 is now also known as an effective stimulator of TH1 immune cells, natural killer (NK) cells, iNKT cells, and CD8 T lymphocytes. Moreover, IL-33 was shown to play an important role in several cancers due to its pro and anti-tumorigenic functions. Currently, IL-33 is a possible inducer and prognostic marker of cancer development with a direct effect on tumor cells promoting tumorigenesis, proliferation, survival, and metastasis. IL-33 also promotes tumor growth and metastasis by remodeling the tumor microenvironment (TME) and inducing angiogenesis. IL-33 favors tumor progression through the immune system by inducing M2 macrophage polarization and tumor infiltration, and upon activation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) or regulatory T cells. The anti-tumor functions of IL-33 also depend on infiltrated immune cells displaying TH1 responses. This review therefore summarizes the dual role of this cytokine in cancer and suggests that new proposals for IL-33-based cancer immunotherapies should be considered with caution
nwCompare and AutoCompare Softwares for Proteomics and Transcriptomics Data Mining â Application to the Exploration of Gene Expression Profiles of Aggressive Lymphomas
chapitre 22International audienc
A Functional γΎTCR/CD3 Complex Distinct from γΎT Cells Is Expressed by Human Eosinophils
BACKGROUND:Eosinophils are effector cells during parasitic infections and allergic responses. However, their contribution to innate immunity has been only recently unravelled. METHODOLOGY/PRINCIPAL FINDINGS:Here we show that human eosinophils express CD3 and gammadelta T Cell Receptor (TCR) but not alphabeta TCR. Surface expression of gammadeltaTCR/CD3 is heterogeneous between eosinophil donors and inducible by mycobacterial ligands. Surface immunoprecipitation revealed expression of the full gammadeltaTCR/CD3 complex. Real-time PCR amplification for CD3, gamma and delta TCR constant regions transcripts showed a significantly lower expression in eosinophils than in gammadeltaT cells. Limited TCR rearrangements occur in eosinophils as shown by spectratyping analysis of CDR3 length profiles and in situ hybridization. Release by eosinophils of Reactive Oxygen Species, granule proteins, Eosinophil Peroxidase and Eosinophil-Derived Neurotoxin and cytokines (IFN-gamma and TNF-alpha) was observed following activation by gammadeltaTCR-specific agonists or by mycobacteria. These effects were inhibited by anti-gammadeltaTCR blocking antibodies and antagonists. Moreover, gammadeltaTCR/CD3 was involved in eosinophil cytotoxicity against tumor cells. CONCLUSIONS/SIGNIFICANCE:Our results provide evidence that human eosinophils express a functional gammadeltaTCR/CD3 with similar, but not identical, characteristics to gammadeltaTCR from gammadeltaT cells. We propose that this receptor contributes to eosinophil innate responses against mycobacteria and tumors and may represent an additional link between lymphoid and myeloid lineages
CĂąncer de fĂgado: ameaça nova ou antiga para os jovens dos paĂses em desenvolvimento?
Among the most frequent malignancies worldwide, hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death (1). Its incidence has doubled over the past two decades, with the greatest burden occurring in low- and middle-income countries. Malignant primary liver tumors are usually described as a pathology affecting mainly men older than 40 years with a cirrhotic liver; they have rarely been reported in younger people and usually, in those younger than 40, most commonly hepatoblastoma.Entre las neoplasias malignas mĂĄs frecuentes del mundo, el carcinoma hepatocelular (CHC) es la segunda causa de muerte relacionada con el cĂĄncer (1). Su incidencia se ha duplicado durante las dos Ășltimas dĂ©cadas y la mayor carga se produce en los paĂses de ingresos bajos y medianos. Los tumores hepĂĄticos primarios malignos suelen describirse como una patologĂa que afecta principalmente a hombres mayores de 40 años con un hĂgado cirrĂłtico; rara vez se han registrado en personas mĂĄs jĂłvenes y normalmente, en menores de 40, lo mĂĄs comĂșn es el hepatoblastoma.Entre as doenças malignas mais comuns no mundo inteiro, o carcinoma hepatocelular (HCC) Ă© a segunda principal causa de morte relacionada ao cĂąncer (1). Sua incidĂȘncia dobrou nas Ășltimas duas dĂ©cadas, sendo que a maior carga ocorreu em paĂses de baixa e mĂ©dia renda. Os tumores primĂĄrios malignos do fĂgado sĂŁo geralmente descritos como uma patologia que afeta principalmente homens acima de 40 anos de idade com fĂgado cirrĂłtico; raramente foram relatados em pessoas mais jovens e geralmente, naqueles com menos de 40 anos, o mais comum Ă© o hepatoblastoma
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