Lactobacilli are probiotics that, among other health promoting effects, have been ascribed immunostimulating and virus preventive properties. Certain lactobacilli species have been shown to possess strong IL-12 inducing properties. As IL-12 production depends on the up-regulation of type I interferons, we hypothesized that the strong IL-12 inducing capacity of L. acidophilus NCFM in murine bone marrow derived DC is caused by an up-regulation of IFN-, which subsequently stimulates the induction of IL-12 and the dsRNA binding toll like receptor (TLR)-3. The expression of the genes encoding IFN-, IL-12, IL-10 and TLR-3 in DC upon stimulation with L. acidophilus NCFM was measured. L. acidophilus NCFM induced a much stronger expression of ifn-, il-12 and il-10 compared to the synthetic dsRNA ligand Poly I:C, whereas the levels of expressed tlr-3 were similar. By the use of whole genome microarray gene expression, we investigated whether other genes related to the viral defence were up-regulated in DC upon stimulation with L. acidophilus NCFM and found that various virus defence related genes, both early and late, were among the strongest up-regulated genes. The IFN- stimulating capability was also detected in another L. acidophilus strain, but was not a property of other probiotic bacteria tested (B. bifidum and E. coli nissle).The IFN- inducing capacity was markedly reduced in TLR-2 -/- DCs, dependent on endocytosis and the major cause of the induction of il-12 and tlr-3 in L. acidophilus NCFM stimulated cells. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DC in a TLR-2 manner through induction of IFN- .
Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism.
Treatment, Time
View SamplesDendritic cells (DC) play a pivotal regulatory role in activation of the innate as well as the adaptive part of the immune system by responding to environmental microorganisms. We have previously shown that some lactobacilli strains induce a strong production of the pro-inflammatory and Th1 polarizing cytokine IL-12 in DC. Contrary, bifidobacteria do not induce IL-12, but are able to inhibit the IL-12 production induced by lactobacilli. In the present study, genome wide microarrays were used to investigate the maturation and gene expression pattern murine bone marrow derived DC stimulated with Lactobacillus acidophilus NCFM and Bifidobacterium bifidum Z9. L. acidophilus NCFM strongly induced expression of interferon (IFN)-, multiple virus defence genes, and cytokine and chemokine genes related to both the adaptive and the innate immune response. Contrary, B. bifidum Z9 mostly up-regulated genes encoding cytokines and chemokines related to the innate immune response. Moreover, B. bifidum Z9 inhibited the expression of the genes initiating the adaptive immune response induced by L. acidophilus NCFM and had an additive effect on genes of the innate immune response and some Th2 skewing genes. The gene encoding Jun dimerization protein 2 (JDP2), a key regulator in cell signalling, was one of the few genes only induced by B. bifidum Z9. Blocking of the JNK1/2 pathway completely inhibited the gene expression of Ifn-. We suggest that B. bifidum Z9 employs an active mechanism to inhibit induction of genes in DC triggering the adaptive immune system and that JPD2 is involved in the regulatory mechanism.
Bifidobacterium bifidum actively changes the gene expression profile induced by Lactobacillus acidophilus in murine dendritic cells.
Specimen part, Treatment
View SamplesPilocytic astrocytoma is the most common type of brain tumor in pediatric population, generally connected with favorable prognosis, although recurrences or dissemination sometimes are also observed. For tumors originating in supra- or infratentorial location different molecular background was suggested but plausible correlations between transcriptional profile and radiological features and/or clinical course are still undefined. The purpose of this study was to identify gene expression profiles related to the most frequent locations of this tumor, subtypes based on various radiological features and clinical pattern of the disease. According to the radiological features presented on MRI, all cases were divided into four subtypes: solid or mainly solid, cystic with an enhancing cyst wall, cystic with a non-enhancing cyst wall and solid with central necrosis. Bioinformatic analyses showed that gene expression profile of pilocytic astrocytoma highly depends on the tumor location. Most prominent differences were noted for IRX2, PAX3, CXCL14, LHX2, SIX6, CNTN1 and SIX1 genes expression which could distinguish pilocytic astrocytomas of different location even within supratentorial region. Analysis of the genes potentially associated between radiological features showed much weaker transcriptome differences. Single genes showed association with the tendency to progression. Here we showed that pilocytic astrocytomas of three different locations could be precisely differentiated on the basis of gene expression level but their transcriptional profiles did not strongly reflect the radiological appearance of the tumor or the course of the disease.
Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features.
Sex, Age, Specimen part, Disease
View SamplesWe have analyzed, using DNA microarrays, putative differences in gene-expression level between hereditary BRCA1 mutation-linked and sporadic breast cancer. Our results show that a previously reported marked difference between BRCA1-mutation linked and sporadic breast cancer was probably due to uneven stratification of samples with different ER status and basal-like versus luminal-like subtype. We observed that apparent difference between BRCA1-linked and other types of breast cancer found in univariate analysis was diminished when data were corrected for ER status and molecular subtype in multivariate analyses. In fact, the difference in gene expression pattern of BRCA1-mutated and sporadic cancer is very discrete. These conclusions were supported by the results of Q-PCR validation. We also found that BRCA1 gene inactivation due to promoter hypermethylation had similar effect on general gene expression profile as mutation-induced protein truncation. This suggests that in the molecular studies of hereditary breast cancer, BRCA1 gene methylation should be recognized and considered together with gene mutation.
BRCA1-related gene signature in breast cancer: the role of ER status and molecular type.
Age
View SamplesMolecular mechanisms of cell cycle exit are poorly understood. A group of genes required for cell cycle exit and maintenance of cell quiescence in human fibroblasts following serum deprivation has been recently identified. Studies on lymphocytes following growth factor deprivation-induced cell cycle exit have predominantly focused on the initiation of apoptosis. A set of genes involved in lymphocyte quiescence have also been identified among genes highly expressed in resting lymphocytes and down-regulated after cell activation. In our study, proliferating IL-2-dependent human T cells were forced to exit cell cycle by growth factor withdrawal, and their gene expression profiles were examined.
Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal.
No sample metadata fields
View SamplesThe introduction of microarray techniques to cancer research brought great expectations for finding biomarkers that would improve patients treatment; however, the results of such studies are poorly reproducible and critical analyses of these methods are rare. In this study, we examined global gene expression in 97 ovarian cancer samples. Also, validation of results by quantitative RT-PCR was performed on 30 additional ovarian cancer samples. We carried out a number of systematic analyses in relation to several defined clinicopathological features. The main goal of our study was to delineate the molecular background of ovarian cancer chemoresistance and find biomarkers suitable for prediction of patients prognosis. We found that histological tumor type was the major source of variability in genes expression, except for serous and undifferentiated tumors that showed nearly identical profiles. Analysis of clinical endpoints [tumor response to chemotherapy, overall survival, disease-free survival (DFS)] brought results that were not confirmed by validation either on the same group or on the independent group of patients. CLASP1 was the only gene that was found to be important for DFS in the independent group, whereas in the preceding experiments it showed associations with other clinical endpoints and with BRCA1 gene mutation; thus, it may be worthy of further testing. Our results confirm that histological tumor type may be a strong confounding factor and we conclude that gene expression studies of ovarian carcinomas should be performed on histologically homogeneous groups. Among the reasons of poor reproducibility of statistical results may be the fact that despite relatively large patients group, in some analyses one has to compare small and unequal classes of samples. In addition, arbitrarily performed division of samples into classes compared may not always reflect their true biological diversity. And finally, we think that clinical endpoints of the tumor probably depend on subtle changes in many and, possibly, alternative molecular pathways, and such changes may be difficult to demonstrate.
Gene expression analysis in ovarian cancer - faults and hints from DNA microarray study.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BRAFV600E-Associated Gene Expression Profile: Early Changes in the Transcriptome, Based on a Transgenic Mouse Model of Papillary Thyroid Carcinoma.
Sex, Age
View SamplesBRAFV600E mutation is the most frequent molecular event in papillary thyroid carcinoma. The relation of this genetic alteration with the factors od poor prognosis has been reported as well as its influence on PTC gene signature. However human material disables distinction of cancer causes from its effect.
BRAFV600E-Associated Gene Expression Profile: Early Changes in the Transcriptome, Based on a Transgenic Mouse Model of Papillary Thyroid Carcinoma.
Sex, Age
View SamplesBRAFV600E mutation is the most frequent molecular event in papillary thyroid carcinoma. The relation of this genetic alteration with the factors od poor prognosis has been reported as well as its influence on PTC gene signature. However human material disables distinction of cancer causes from its effect.
BRAFV600E-Associated Gene Expression Profile: Early Changes in the Transcriptome, Based on a Transgenic Mouse Model of Papillary Thyroid Carcinoma.
Sex, Age
View SamplesThyroid gland is among the most sensitive organs to ionizing radiation. Whether low-dose radiation-induced papillary thyroid cancer (PTC) differs from sporadic PTC is yet unknown.
Gene signature of the post-Chernobyl papillary thyroid cancer.
No sample metadata fields
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