GSE148278 Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and through secondary effects ATAC-seq

Contributors : Spencer Arnesen ; Jason GertzSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensWhile breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER’s actions, a significant number relapse. Approximately 30% of these recurrences harbor activating mutations in ER’s ligand binding domain. ER mutations have been shown to confer ligand-independent function to ER; however, much is still unclear regarding the effect of mutant ER beyond its estrogen independence. To investigate mutant ER’s molecular effects, we developed multiple isogenic ER mutant cell lines for the two most common ER ligand binding domain mutations, Y537S and D538G. We found that these mutations induce diff erential expression of thousands of genes, the majority of which are specific to one or the other mutation and are not observed upon estrogen treatment of wildtype cells. The mutant-specific genes show consistent differential expression across ER mutant lines developed in other laboratories. The obs erved gene expression changes cannot be explained by constitutive ER activity alone, as wildtype cells with long term estrogen exposure only exhibit some of these transcriptional changes, suggesting that mutant ER causes novel regulatory effects that are not simply due to constant activity. While ER mutations have minor effects on ER genomic binding, with the ex...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research

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Publication date: Available online 4 June 2020Source: Annals of Medicine and SurgeryAuthor(s): Yasser El Ghamrini, Tamer M.S. Salama, Mohamed I. Hassan, Haytham Mohamed Nasser
Source: Annals of Medicine and Surgery - Category: General Medicine Source Type: research
This study shows the complexity of genetic variation in predicting outcomes to treatment. We advocate for future replicative studies to potentially validate GSTA1 and CYP2C19 and definitively negate CYP3A4 and GSTP1 as biomarkers for risk of CROF after cyclophosphamide treatment. Understanding genetic variation in chemotherapy metabolism has the potential to individualise treatment regimens to maximise efficacy and minimise toxicity. PMID: 32496149 [PubMed - as supplied by publisher]
Source: Journal of Obstetrics and Gynaecology - Category: OBGYN Tags: J Obstet Gynaecol Source Type: research
ConclusionsThe use of Kaiser score in high-risk MRI screening reliably excludes malignancy in more than 45% of contrast-enhancing lesions classified as BI-RADS 4.Key Points•The Kaiser score shows high diagnostic accuracy in identifying malignancy in contrast-enhancing lesions in patients undergoing high-risk screening for breast cancer.•The application of the Kaiser score may avoid> 45% of unnecessary breast biopsies in high-risk patients.•The Kaiser score aids decision-making in high-risk breast cancer MRI screening programs.
Source: European Radiology - Category: Radiology Source Type: research
Publication date: 24 September 2020Source: Inorganica Chimica Acta, Volume 510Author(s): Thankaraj Salammal Sheena, Rajakumaran Dhivya, Venkatesan Rajiu, K. Jeganathan, Mallayan Palaniandavar, Ganesan Mathan, Mohammad Abdulkader Akbarsha
Source: Inorganica Chimica Acta - Category: Chemistry Source Type: research
Authors: Ao H, Li Y, Li H, Wang Y, Han M, Guo Y, Shi R, Yue F, Wang X Abstract Hydroxy genkwanin (HGK), a flavonoid compound from natural resources, showed good inhibition against the growth of breast tumor cells. However, the poor solubility restricted the further study and the in vivo drug delivery of HGK. We prepared HGK nanosuspensions by antisolvent precipitation method and investigated their characterization, stability, hemolysis probability, release behavior in vitro, antitumor activity in vitro and in vivo, and preliminary safety through acute toxicity experiments. The resultant HGK nano...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research
Authors: Macruz CF, Lima SMRR, Postigo S, Martins MM, Lucarelli AP, de Oliveira VM Abstract OBJECTIVE: To assess quality of life and climacteric symptoms for post-menopausal women receiving hormone therapy for breast cancer. METHODS: A prospective observational study of women treated at the Mastology Outpatient Clinic of the Department of Obstetrics and Gynecology was conducted between 2015 and 2019. Post-menopausal patients who had been diagnosed with breast cancer and who were experiencing climacteric symptoms were selected. These patients had undergone surgery, radiotherapy, and/or chemotherapy more than one...
Source: Journal of Obstetrics and Gynaecology Canada : JOGC - Category: OBGYN Tags: J Obstet Gynaecol Can Source Type: research
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Source: Pathology Research and Practice - Category: Pathology Source Type: research
Condition:   HER2-positive Breast Cancer Interventions:   Drug: Docetaxel;   Drug: Carboplatin;   Drug: Trastuzumab;   Drug: Pertuzumab;   Drug: Trastuzumab emtansine Sponsor:   University of Rochester Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Anatomic Stage IV Breast Cancer AJCC v8;   Metastatic Breast Carcinoma;   Prognostic Stage IV Breast Cancer AJCC v8;   Recurrent Breast Carcinoma;   Refractory Breast Carcinoma Interventions:   Drug: Cyclophosphamide;   Biological: Allogeneic GM-CSF-secreting Breast Cancer Vaccine SV-BR-1-GM;   Biological: Pembrolizumab;   Biological: Recombinant Interferon Alpha 2b-like Protein;   Other: Questionnaire Administration;   Other: Quality of...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Triple Negative Breast Cancer Interventions:   Drug: epirubicin hydrochloride;   Drug: Cyclophosphamide;   Drug: Albumin bound paclitaxel;   Drug: Toripalimab Sponsor:   Fudan University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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