Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA140143 | ENA |
REPOSITORIES: ENA
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Project description:Five years of tamoxifen reduces breast cancer risk by nearly 50% but is associated with significant side-effects and toxicities. A better understanding of the direct and indirect effects of tamoxifen in benign breast tissue could elucidate new mechanisms of breast carcinogenesis, suggest novel chemoprevention targets, and provide relevant early response biomarkers for Phase II prevention trials. Seventy-three women at increased risk for breast cancer were randomized to tamoxifen (20 mg daily) or placebo for three months. Blood and breast tissue samples were collected at baseline and post-treatment. Sixty-nine women completed all study activities (37 tamoxifen and 32 placebo). The selected biomarkers focused on estradiol and IGFs in the blood, DNA methylation and cytology in random periareolar fine needle aspirates, and tissue morphometry, proliferation, apoptosis, and gene expression (microarray and RT-PCR) in the tissue core samples. Tamoxifen downregulated ets-oncogene family members ETV4 and ETV5 and reduced breast epithelial cell proliferation independent of CYP2D6 genotypes or effects on estradiol, ESR1 or IGFs. Reduction in proliferation was correlated with downregulation of ETV4 and DNAJC12. Tamoxifen also modulated expression of RAB GTPases, and several genes involved in epithelial-stromal interaction, and reduced tumor suppressor gene methylation. Three months of tamoxifen did not affect breast tissue composition, cytological atypia, preneoplasia or apoptosis. Tamoxifen may durably reduce breast cancer risk through downregulation of ETV4 and ETV5 which could deplete mammary progenitor populations. This pathway has the potential to provide novel targets and early response biomarkers for phase II prevention trials. Randomized prospective double blinded placebo-controlled trial of tamoxifen (20 mg daily) versus placeo in women at increased risk for breast cancer. Gene expression was assessed in whole breast tissue cores obtained at baseline and after three months of treatment for 35 women. Core biopsies were obtained in the late luteal phase (day 28 +/- 2) for premenopausal women (N = 19). Breast lobules from the baseline and post-treatment cores were microdissected for 5 tamoxifen subjects.
2011-07-21 | E-GEOD-29338 | biostudies-arrayexpress
Project description:Five years of tamoxifen reduces breast cancer risk by nearly 50% but is associated with significant side-effects and toxicities. A better understanding of the direct and indirect effects of tamoxifen in benign breast tissue could elucidate new mechanisms of breast carcinogenesis, suggest novel chemoprevention targets, and provide relevant early response biomarkers for Phase II prevention trials. Seventy-three women at increased risk for breast cancer were randomized to tamoxifen (20 mg daily) or placebo for three months. Blood and breast tissue samples were collected at baseline and post-treatment. Sixty-nine women completed all study activities (37 tamoxifen and 32 placebo). The selected biomarkers focused on estradiol and IGFs in the blood, DNA methylation and cytology in random periareolar fine needle aspirates, and tissue morphometry, proliferation, apoptosis, and gene expression (microarray and RT-PCR) in the tissue core samples. Tamoxifen downregulated ets-oncogene family members ETV4 and ETV5 and reduced breast epithelial cell proliferation independent of CYP2D6 genotypes or effects on estradiol, ESR1 or IGFs. Reduction in proliferation was correlated with downregulation of ETV4 and DNAJC12. Tamoxifen also modulated expression of RAB GTPases, and several genes involved in epithelial-stromal interaction, and reduced tumor suppressor gene methylation. Three months of tamoxifen did not affect breast tissue composition, cytological atypia, preneoplasia or apoptosis. Tamoxifen may durably reduce breast cancer risk through downregulation of ETV4 and ETV5 which could deplete mammary progenitor populations. This pathway has the potential to provide novel targets and early response biomarkers for phase II prevention trials.
2011-07-22 | GSE29338 | GEO
Project description:Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial validates low estrogen receptor mRNA level as the main determinant of tamoxifen resistance in estrogen receptor positive breast cancer. In NSABP Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the incidence of estrogen receptor (ER) positive tumors but not estrogen receptor negative breast cancer. More importantly, only 69% of estrogen receptor positive tumors were prevented by tamoxifen. The ER positive tumors arising in tamoxifen arm provides an ideal clinical model for acquired tamoxifen resistance. Based on data from NSABP trial B14 which showed linear prediction of the degree of benefit from adjuvant tamoxifen by the levels of ESR1 mRNA coding for ER-alpha, we hypothesized a priori that level of ESR1 mRNA would be lower in ER positive tumors arising in tamoxifen arm compared to those in placebo arm of BCPT. Keywords: Gene expression profiling analysis Formalin fixed paraffin embedded tumor blocks with enough tumor tissue for RNA extraction were available from 108 cases (69 from placebo arm and 39 from tamoxifen arm) of the 264 that experienced invasive breast cancer (175 in placebo arm and 89 in tamoxifen arm) in BCPT before unblindings . Central ER immunohistochemistry identified 84 of them as ER positive (57 from placebo arm and 27 from tamoxifen arm). A novel protocol was developed and used to obtain microarray gene expression profiling from the degraded or fragmented RNA extracted from formalin fixed paraffin blocks.Hybridization intensity data were compiled using Partek Genomic Suite. After quantile normalization, genes with mean intensity below 500 were filtred out, which left 7743 probes with informative data. Data were log2 transformed for statistical analysis.
2011-12-08 | E-GEOD-12665 | biostudies-arrayexpress
Project description:Adjuvant tamoxifen is a valid treatment option for women with estrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response. We performed a global microRNA screen in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence. Patients were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005.
2014-07-01 | GSE46823 | GEO
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:We analyzed gene expression in human peripheral blood mononuclear cells (PBMCs) from breast cancer patients, patients with benign breast abnormalities, healthy cancer-free individuals as well as patients with other types of cancer (gastrointestinal and brain cancers). Peripheral blood mononuclear cell (PBMC) samples were collected from women with a suspect initial mammogram prior to undergoing a diagnostic biopsy procedure to determine whether the detected abnormality was benign or malignant. In total, we collected blood from 57 women with a diagnosis of breast cancer and 37 with a benign diagnosis. We also collected blood from 31 women with normal initial mammograms as negative controls and 15 breast cancer patients following surgery. All breast cancer patient samples were collected at the Duke University Medical Center (DUMC) under an institutional review board (IRB)-approved protocol (Duke eIRB#12025) after obtaining informed consent and were provided by Dr. Jeffrey Marks. PBMC samples from patients with various gastrointestinal cancers (n=15) were colelcted and stored at DUMC under IRB-approved protocols (Duke eIRB#12010 and 12025) and were provided by Dr. Jeffrey Marks. Peripheral blood leukocyte samples from patients with brain tumors (n=7) were provided by Dr. John Sampson and were collected by leukapheresis under Duke eIRB#00003877 and #00009403.
2011-03-01 | E-GEOD-27562 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4686780 | biostudies-literature
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
2014-12-02 | GSE63741 | GEO
Project description: Not available
| S-EPMC3743458 | biostudies-literature