7300 results for "canc*"

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• Combined MEK and BCL-2/XL inhibition is effective in high-grade serous ovarian cancer patient-derived xenograft models and BIM levels are predictive of responsiveness

  Most patients with late stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, thus making it an attractive therapeutic target. Here, we systematically evaluated the extent of MEK/ERK pathway activation and efficacy of pathway inhibition in a large panel of well-annotated HGSOC patient-derived xenograft (PDX) models. The vast majority of models were nonresponsive to the MEK inhibitor cobimetinib (GDC-0973) despite effective pathway inhibition. Proteomic analyses of adaptive responses to GDC-0973 revealed that GDC-0973 upregulated the pro-apoptotic protein BIM, thus priming the cells for apoptosis regulated by BCL2-family proteins. Indeed, combination of both MEK inhibitor and dual BCL-2/XL inhibitor (ABT-263) significantly reduced cell number, increased cell death and displayed synergy in vitro in most models. In vivo, the GDC-0973 and ABT-263 combination was well tolerated and resulted in greater tumor growth inhibition than single agents. Detailed proteomic and correlation analyses identified two subsets of responsive models – those with high BIM at baseline that was increased with MEK inhibition and those with low basal Bim and high pERK levels. Models with low BIM and low pERK were non-responsive. Our findings demonstrate that combined MEK and BCL-2/XL inhibition has therapeutic activity in HGSOC models and provide a mechanistic rationale for clinical evaluation of this drug combination as well as the assessment of the extent to which BIM and/or pERK levels predict drug combination effectiveness in chemoresistant HGSOC.

  Dataset EGAD00001005111

• Gene expression profile of mesothelial-derived carcinoma-associated fibroblasts

  RNA-sequencing was carried out on ascetic fluid-isolated mesothelial cells from low-grade serous ovarian cancer patients, high-grade serous ovarian cancer patients, chemotherapy-treated high-grade serous ovarian cancer patients and control mesothelial cells obtained from non-oncologic patients to identify differentially expressed genes associated to mesothelial-to-mesenchymal transition process. The dataset contains 18 samples: - Control mesothelial cells: 4 samples - Group 1, high-grade serous ovarian cancer patients: 3 samples - Group 2, chemotherapy-treated high-grade serous ovarian cancer patients: 5 samples - Group 3, low-grade serous ovarian cancer patients: 6 samples

  Dataset EGAD00001005133

• Next gen seq of eye cancers (2019-08-14)

  Retinoblastoma (RB), the commonest eye cancer in children was the first cancer for which a genetic cause was identified: the Rb1 gene is a tumour suppressor gene that is mutated in RB. The Rb1 gene defect alone does not predict the clinical outcome. We propose to study other possible mechanisms: 1. Stepwise further mutations occur in RB, increasing its carcinogenesis. We will sequence the whole genome in RB tissue, and relate the different genes expressed to the treatments used. 2. Extracellular matric proteins contribute to a tumour permissive environment for RB to continue to grow. This includes Samll Leucine Rich Proteoglycans (SLRP), a family of 15 secreted extracellular matrix proteins involved in eye development. 3. Cancer stem cells (CSC), a subpopulation of treatment resistant cells, drive RB tumours, and whether these stem cells can be manipulated for new therapies. The aim of this study is to assist finding targeted diagnostic techniques and treatments for RB. . This dataset contains all the data available for this study on 2019-08-14.

  Dataset EGAD00001005251

• Predictor_ChemoNEAR_TNBC (2019-08-14)

  In this study a collection of core biopsies from breast cancer patients receiving neoadjuvant chemotherapy as part of the ChemoNEAR trial will be investigated. The study is intended to detect early acquired resistance in women with diagnosed breast carcinoma. Samples will undergo whole genome sequencing and analysis, including use of HR Predict. . This dataset contains all the data available for this study on 2019-08-14.

  Dataset EGAD00001005255

• Genomic variants in 121 genes associated with ovarian cancer in cancer tissue and derived organoids

  High-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium, but advanced stages are mostly found outside the FT. We used ex-vivo cultures of HGSOC and knock-out of tumor suppressors in FT organoids to study changes in epithelial cells and niche requirements for normal and transformed FT cells. We found that transformed cells require BMP signaling and are growth arrested in Wnt rich medium. A SureSelectXT Automation Custom Capture Library (Agilent) target enrichment panel was designed. The enrichment panel comprised all coding exons of 121 genes associated with ovarian cancer. Capture was performed according to the manufacturer’s instructions using an NGS Workstation Option B (Agilent) for automated library preparation starting with 3 μg DNA per sample. Sequencing was performed on a Illumina Hiseq 2500 system gnerating 2x100bp paired end reads and a target coverage of >200 per sample. Sequence reads were mapped to the haploid human reference genome (hg19) using BWA. Variants where called with FreeBayes v1.1.

  Dataset EGAD00001005279

• Deep multi-region WGS of lung cancer tumours

  Deep WGS (germline and 2-5 tumour regions) was performed on 20 patients: 13 lung adenocarcinoma, 5 squamous cell carcinoma, 2 small-cell lung cancers. A total of 68 BAM files are provided, where tumours were sequenced to 60x or 150x depth.

  Dataset EGAD00001005287

• LINE luminal breast cancer Neoadjuvant Chemotherapy Study (2019-08-28)

  A targeted gene screen of 365 known cancer genes in luminal breast cancer samples pre-chemotherapy and at resection post-chemotherapy to evalaute clonal expansion of chemotherapy cancer cells. . This dataset contains all the data available for this study on 2019-08-28.

  Dataset EGAD00001005297

• Long-read WGS of three cancer cell lines

  Long-read WGS of three cancer cell lines

  Dataset EGAD00001005184

• Patient-derived lung cancer organoids

  Patient-derived lung cancer organoids cram files : targeted seq 13 samples, whole exome seq 12 samples mutation profiles of PDO and matched tissue : aggregated vcf 1 file details : https://www.nature.com/articles/s41467-019-11867-6

  Dataset EGAD00001005317

• Exome and Transcriptome for gynecologic cancer gene-drug analysis

  Total of 180 gynecologic tumor specimens were subjected for targeted-exome and/or whole-transcriptome sequencing.

  Dataset EGAD00001005331