Project description:To identify key genes in the early sex development of zebrafish, we generated zebrafish (AB strain) feminized by sex hormone 17β-estradiol (E2, CAS: 50-28-2, 100 ng/L) and masculinized by aromatase inhibitor exemestane (EM, CAS: 107868-30-4, 10 μg/L), and detected their transcriptomes by RNA-seq.
Project description:We evaluated the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with ER+/HER2− premenopausal MBC who had failed one to two lines of hormone therapy without chemotherapy.
Project description:We evaluated the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with ER+/HER2− premenopausal MBC who had failed one to two lines of hormone therapy without chemotherapy.
Project description:mRNA-seq of zebrafish treated with sex hormone 17β-estradiol and aromatase inhibitor exemestane at 12dpf (mixed species RNA preparation prepared with Drosophila S2 cell RNA)
Project description:To explore the transcriptional effects of aromatase inhibitors on sex differentiation of zebrafish, we exposed 3-month-old zebrafish (AB strain) to the third generation aromatase inhibitor Exemestane (CAS: 107868-30-4) and characterized transcript abundance among testes and ovaries after 32 days of drug exposure. After the drug treatment, we dissected zebrafish gonads, isolated polyA+ RNA and performed high-throughput RNA-Seq analysis.
Project description:Identification and relative quantification of proteins associated with substance specific alterations and sex-specific physiological responses following aromatase inhibition.
Project description:MCF-7aro cells were used to generate a cell culture model system that is resistant to 3 aromatase inhibitors (AIs), letrozole, anastrozole and exemestane. For comparison, the MCF-7aro cells were also used to generate the tamoxifen-resistant cells as well as long-term estrogen deprived, LTEDaro. Affymetrix microarray analysis was performed to determine changes in gene expression that are unique to AI-resistance. Experiment Overall Design: For control purposes, MCF-7aro cells were cultured without any hormone or inhibitor as well as a hormone-only control (T-only). Resistant cells were grown in the presence of testosterone, T+LET R (letrozole), T+ANA R (anastrozole), T+EXE R (exemestane), T+TAM R (Tamoxifen). In addition, testosterone-free resistant lines were generated, LTEDaro, ANA R and EXE R. 6 replicates were generated for the hormone-containing resistant lines and 3 replicates for the hormone-free resistant lines.
Project description:In the present study transcriptome analysis was employed to investigate the early molecular responses to exposure to 17β-estradiol (CAS 50-28-2). Zebrafish embryos were exposed to 17β-estradiol according to OECD guidelines (OECD test No. 236). At the end of exposure time (96 hours), simultaneous RNA and protein extraction from 10 embryos was performed using a Macherey & Nagel RNA/protein extraction kit. The obtained RNA extracts were sequenced using Illumina NovaSeq 6000 system System and the obtained sequences went through bioinformatic analysis pipeline to Identify and count the detected gene sequences followed by differential gene expression analysis. Finally, potential substance specific biomarker candidates were refined and selected based on the differential expression patterns and the biological functions investigation of the detected DEGs.
