Conditional knockout of Snai1 in the mouse intestinal epithlium results in apoptotic loss of crypt base columnar cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snail conditional knockout mice also undergo apoptosis when Snai1 is deleted.
Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.
No sample metadata fields
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 SamplesBackground: The insulin/IGF/relaxin family represents a group of structurally related but functionally diverse proteins. The family member Relaxin-2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of Insulin-like peptide 6 (Insl6), another member of this protein family, in murine heart failure models using genetic loss-of-function and protein delivery methods. Methods and Results: Insl6-deficient (Insl6-KO) and wild-type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively for 2 weeks. In both models, Insl6-KO mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation hypertrophy. Cardiac dysfunction in the Insl6-KO mice was associated with more extensive cardiac fibrosis and greater expression of fibrosis-associated genes. The continuous infusion of chemically synthesized INSL6 significantly attenuated left ventricular systolic dysfunction and cardiac fibrosis induced by isoproterenol infusion. Gene expression profiling suggests Lxr/ Rxr signaling is activated in the isoproterenol-challenged hearts treated with INSL6 protein. Conclusions: Endogenous Insl6 protein inhibits cardiac systolic dysfunction and cardiac fibrosis in angiotensin II- and isoproterenol-induced cardiac stress models. The administration of recombinant Insl6 protein could have utility for the treatment of heart failure and cardiac fibrosis.
Relaxin Family Member Insulin-Like Peptide 6 Ameliorates Cardiac Fibrosis and Prevents Cardiac Remodeling in Murine Heart Failure Models.
Sex, Specimen part, Treatment
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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