Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine.
Epigenetic silencing of novel tumor suppressors in malignant melanoma.
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Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Specimen part, Time
View SamplesTo determine what DNA methylation and gene expression changes occur following EBV transformation. B-cells were isolated from 3 donors. Resting, CD40 activated and EBV transfromed cells from each donor was analyzed. Each sample was assayed using Affymetrix expression arrays and whole genome bisulfite sequenicng. Additional time points during transformation and activation were sequenced as well, but not assayed for expression.
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection.
Age, Specimen part, Compound
View SamplesIt is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used vaginal biopsies from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations.
Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection.
Age, Specimen part, Compound
View SamplesIt is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used ectocervical biopsies from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations.
Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection.
Age, Specimen part, Compound
View SamplesIt is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used peripheral blood mononuclear cells from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations.
Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection.
Age, Specimen part, Compound
View SamplesIt is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used cervicovaginal biopsies from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations. The samples in this series are thought to be endocervical biopsies on the basis of their gene expression.
Treatment with Commonly Used Antiretroviral Drugs Induces a Type I/III Interferon Signature in the Gut in the Absence of HIV Infection.
Age, Specimen part, Compound
View SamplesExpression profiling was performed using uncultured melanocytes and melanoma cell from various mouse models of BrafV600E induced melanocytic proliferation
mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation.
Specimen part
View SamplesThe LH surge triggers dramatic transcriptional changes in genes associated with ovulation and luteinization. The present study investigated the spatiotemporal expression of nuclear factor interleukin-3 (NFIL3), a transcriptional regulator of the bZIP transcription factor superfamily, and its potential role in the ovary during the periovulatory period. NFIL3, also known as E4-binding protein 4 or NFIL3/E4BP4, was originally identified as a transcriptional repressor based on its DNA-binding activity at the promoter of the gene encoding the adenovirus E4 protein. Immature female rats were injected with PMSG, treated with hCG, and ovaries or granulosa cells were collected at various times after hCG. Nfil3 mRNA was highly induced both in intact ovaries and granulosa cells after hCG treatment. In situ hybridization demonstrated that Nfil3 mRNA was highly induced in theca-interstitial cells at 4-8 h after hCG, localized to granulosa cells at 12 h, and decreased at 24 h. Over-expression of NFIL3 in granulosa cells inhibited the induction of prostaglandin-endoperoxide synthase 2 (Ptgs2), progesterone receptor (Pgr), epiregulin (Ereg), and amphiregulin (Areg) and down regulated levels of prostaglandin E2. The inhibitory effect on Ptgs2 induction was reversed by NFIL3 siRNA treatment. In theca-interstitial cells the expression of hydroxyprostaglandin dehydrogenase 15-(NAD) (Hpgd) was also inhibited by NFIL3 over-expression. Data from luciferase assays demonstrated that NFIL3 over-expression decreased the induction of the Ptgs2 and Areg promoter activity. EMSA and ChIP analyses indicated that NFIL3 binds to the promoter region containing the DNA binding sites of CREB and C/EBP?. In summary, hCG induction of NFIL3 expression may modulate the process of ovulation and theca-interstitial and granulosa cell differentiation by regulating expression of PTGS2, PGR, AREG, EREG, and HPGD, potentially through interactions with CREB and C/EBP? on their target gene promoters.
A role for nuclear factor interleukin-3 (NFIL3), a critical transcriptional repressor, in down-regulation of periovulatory gene expression.
Sex
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