High-grade gliomas are amongst the most deadly human tumors. Treatment results are overall disappointing. Nevertheless, in several trials around 20% of patients respond to therapy. Diagnostic strategies to identify those patients that will ultimately profit from a specific targeted therapy are urgently needed. Gene expression profiling of untreated tumors is a well established approach for identifying biomarkers or diagnostic signatures. However, reliable signatures predicting treatment response in gliomas do not exist. Here we suggest a novel strategy for developing diagnostic signatures. We postulate that predictive gene expression patterns emerge only after tumor cells have been treated with the agent in vitro. Moreover, we postulate that enriching specimens for tumor initiating cells sharpens predictive expression patterns. Here, we report on the prediction of treatment response of cancer cells in vitro. As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated but not from untreated glioma cells allowed to predict therapy-induced impairment of proliferation of glioma cells in vitro. Prediction can be achieved with as little as 6 genes allowing for a straightforward translation into the clinic once the predictive power of the signature is shown also in vivo. Our strategy of using expression profiles from in vitro treated BTIC-enriched cultures opens new ways for trial design for patients with malignant gliomas.
Response-predictive gene expression profiling of glioma progenitor cells in vitro.
Specimen part, Treatment
View SamplesMicroarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients.
Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR<sub>mut</sub> NSCLC in diagnosis, follow-up and treatment.
No sample metadata fields
View SamplesBrain inflammation, a common feature in neurodegenerative diseases, is a complex series of events, which can be detrimental and even lead to neuronal death. Nonetheless, several studies suggest that inflammatory signals are also positively influencing neural cell proliferation, survival, migration and differentiation. Recently, correlative studies suggested that astrocytes are able to dedifferentiate upon injury, and may thereby re-acquire neural stem cells (NSC) potential. However, the mechanism underlying this dedifferentiation process upon injury remains unclear. In this study, we find that during the early response of reactive gliosis, inflammation induces a conversion of mature astrocytes into neural progenitors. A TNF treatment induces the decrease of specific astrocyte markers, such as GFAP or genes related to glycogen metabolism, while a subset of these cells re-express immaturity markers, such as CD44, Musashi-1 and Oct4. Thus, TNF treatment results in the appearance of cells that exhibit a neural progenitor phenotype and are able to proliferate and differentiate into neurons and/or astrocytes.
Inflammation Promotes a Conversion of Astrocytes into Neural Progenitor Cells via NF-κB Activation.
Specimen part
View SamplesThe encapsulated yeast Cryptococcus neoformans can cause a fatal meningoencephalitis in immunocompromised patients. C. neoformans infection is acquired through the respiratory tract, but the cellular and molecular mechanisms of the pulmonary innate immune response are still not well defined. To investigate the response of CCR2+ inflammatory monocytes to C. neoformans, we compared the transcriptomes of CCR2+ inflammatory monocytes from the lungs of naïve versus infected mice. Overall design: Sorted pulmonary CCR2+ inflammatory monocytes were pooled from 6-7 CCR2-GFP reporter mice per group, including naïve mice and mice challenged with intratracheal Cryptococcus neoformans on days 5 and 10 post-infection.
Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans.
Specimen part, Cell line, Subject
View SamplesCg.5XFAD females (MMRRC Stock No #34848-JAX) were bred to males from BXD strains. The resulting F1 progeny were monitored throughout their lifepan to evaluate the effect of genetic background on cognitive and pathological traits. Samples here come from various AD-BXD lines at either 6 or 14 months of age. An earlier dataset of similar design (plus Non-transgenic littermates) was deposited as GSE101144. Ntg littermates of mice sampled here will be deposited as a separate GEO series. Overall design: 88 AD samples. For final by-strain analysis, samples were averaged into strain/age/genotype/sex groups (For example, all D2 6mo 5XFAD males were averaged for final by-strain analysis)
Identification of Pre-symptomatic Gene Signatures That Predict Resilience to Cognitive Decline in the Genetically Diverse AD-BXD Model.
Sex, Age, Specimen part, Cell line, Subject
View SamplesFemale C57BL/6J mice hemizygous for the 5XFAD transgene (MMRRC Stock No #34848-JAX) were bred to males from BXD strains, which do not carry the 5XFAD transgene. The resulting F1 progeny were monitored throughout their lifespan to evaluate the effect of genetic background on cognitive and pathological traits. All of the mice were fear conditioned and sacrificed within 30 minutes of testing. On the sample records, the characteristics: age field provides the age at which fear conditioning, sacrifice, and tissue collection occurred. Samples here come from various AD-BXD lines and their non-transgenic (Ntg) littermate counterparts at either 6 or 14 months of age. Overall design: 133 samples, 64 Ntg and 69 AD. For final by-strain analysis, samples were averaged into strain/age/genotype/sex groups (For example, all D2 6mo 5XFAD males were averaged for final by-strain analysis)
Harnessing Genetic Complexity to Enhance Translatability of Alzheimer's Disease Mouse Models: A Path toward Precision Medicine.
Sex, Age, Specimen part, Subject
View SamplesBiopsies from uninvolved and from lesional skin of 13 patients with plaque-type psoriasis. Based on paired samples, 179 genes were more than 2-fold differentially expressed in lesional skin.
Increased expression of Wnt5a in psoriatic plaques.
Sex, Age
View SamplesComparison of gene expression profiles in whole blood collected from pregnant and non-pregnant females.
Placenta-derived fetal specific mRNA is more readily detectable in maternal plasma than in whole blood.
Sex, Specimen part
View SamplesWe expressed either only the E7 oncoprotein or the complete early genome region (CER) of the human papillomavirus type 8 in primary human adult skin keratinocytes.
Novel Insights Into Cellular Changes in HPV8-E7 Positive Keratinocytes: A Transcriptomic and Proteomic Analysis.
Specimen part
View SamplesTo identify the genes and pathways regulated by FOXF2, we investigated potential FOXF2 gene targets by microarray analyses of primary prostate stromal cells (PrSC) in which FOXF2 was knocked down by siRNA. 190 differentially expressed genes were selected, of which 104 genes were more highly expressed in PrSC cells treated with FOXF2 siRNA and 86 were more highly expressed in PRSC cells treated with negative control siRNA.
The FOXF2 pathway in the human prostate stroma.
No sample metadata fields
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