A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)
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PROVIDER: EGAS00001003252 | EGA |
REPOSITORIES: EGA
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Project description:This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.
| EGAD00001004391 | EGA
Project description:This project aimed to map transcriptome changes in the forearm skeletal muscle of patients with chronic kidney disease undergoing hemodialysis access placement surgery. Muscle biopsies were obtained from the brachioradialis muscle pre- and at several timepoints post-operatively.
2026-01-01 | GSE287576 | GEO
Project description:We performed a retrospective analysis of the SweBCG 91-RT trial, which randomized women with node-negative stage I-IIA breast cancer to whole breast radiotherapy or no radiotherapy following breast-conserving surgery with minimal use of adjuvant systemic treatment. Primary tumors were profiled with the GeneChip Human Exon 1.0 ST microarray.
2019-09-26 | GSE119295 | GEO
Project description:Background: Breast cancer patients present lower 1,25(OH)2D3 or 25(OH)D3 serum levels than unaffected women. Although 1,25(OH)2D3 pharmacological concentrations of 1,25(OH)2D3 may exert antiproliferative effects in breast cancer cell lines, much uncertainty remains about the effects of calcitriol supplementation in tumor specimens in vivo. We have evaluated tumor dimension (ultrassonography), proliferative index (Ki67 expression), 25(OH)D3 serum concentration and gene expression profile, before and after a short term calcitriol supplementation (dose to prevent osteoporosis) to post-menopausal patients. Results: Thirty three patients with operable disease had tumor samples evaluated. Most of them (87.5%) presented 25(OH)D3 insufficiency (<30 ng/mL). Median period of calcitriol supplementation was 30 days. Although tumor dimension did not vary, Ki67 immunoexpression decreased after supplementation. Transcriptional analysis of 15 matched pre/post-supplementation samples using U133 Plus 2.0 GeneChip (Affymetrix) revealed 18 genes over-expressed in post-supplementation tumors. As a technical validation procedure, expression of four genes was also determined by RT-qPCR and a direct correlation was observed between both methods (microarray vs PCR). To further explore the effects of near physiological concentrations of calcitriol on breast cancer samples, an ex vivo model of fresh tumor slices was utilized. Tumor samples from another 12 post-menopausal patients were sliced and treated in vitro with slightly high concentrations of calcitriol (0.5nM), that can be attained in vivo, for 24 hours In this model, expression of PBEF1, EGR1, ATF3, FOS and RGS1 was not induced after a short exposure to calcitriol. Conclusions: In our work, most post-menopausal breast cancer patients presented at least 25(OH)D3 insufficiency. In these patients, a short period of calcitriol supplementation may prevent tumor growth and reduce Ki67 expression, probably associated with discrete transcriptional changes. This observation deserves further investigation to better clarify calcitriol effects in tumor behavior under physiological conditions. Post-menopausal patients with early stage breast cancer, in the absence of distant metastasis, were invited to take part in the study. This protocol was approved by the Institutional Ethics Committee, and a written informed consent was signed by all participants. Patients had blood and tumor samples collected during biopsy, and were prescribed calcitriol supplementation, (Rocaltrol)TM 0.50 g/day PO, as recommended for osteoporosis prevention. Tumor specimens obtained during biopsy (pre-supplementation) or breast surgery (post-supplementation) were hand dissected and samples with at least 70% tumor cells were further processed. Breast surgery followed in about one month
2012-02-18 | E-GEOD-35925 | biostudies-arrayexpress
Project description:For successful treatment of breast cancer, early and efficient diagnosis is paramount. However, the diagnosis of breast cancer in the earliest stage, stage 1, is challenging as small tumors are often left undetected by conventional imaging techniques. Additionally, 8 out of 10 breast masses are classified as benign which causes unnecessary psychological stress and increased costs to the medical system. To improve the detection of early-stage breast cancer, development of non-invasive approaches should be explored. Here, we investigated the potential of extracellular vesicles (EVs) to report on a breast cancer diagnosis. EVs contain unique cancer-associated proteins from the parental cell and have the potential to be used for early detection of tumor growth. We isolated EVs from healthy (19), benign (19), and early-stage breast cancer (86) patient plasma samples using size exclusion chromatography. Mass spectrometry analysis identified 94 significantly changed proteins in the plasma EVs from breast cancer patients . Using a cohort of pre- and post-surgery breast cancer patients, we identified enolase 1 as a promising biomarker for breast cancer detection. Enolase 1 was further validated using a larger cohort of healthy and breast cancer patients, by high-throughput ELISA of plasma, and was found to be elevated in breast cancer patient plasma at all stages, including Stage 1. Furthermore, enolase-1 plasma levels decreased post-operatively upon tumor removal. An enolase 1 liquid blood biopsy could be used to support breast cancer screening for the identification of high-risk individuals promoting the diagnosis of breast cancer at the very earliest and treatable stage. Furthermore, plasma-enolase 1 can decipher between individuals with a benign or cancerous mass, it could therefore be used alongside current imaging practices to direct physician decisions to carry out only necessary needle biopsy procedures.
2025-01-31 | MSV000097016 | MassIVE
Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Genome-wide expression analysis was performed on breast cancer tissue from women following treatment with soy (n=28) or placebo (n=23).
2014-07-01 | E-GEOD-58792 | biostudies-arrayexpress
Project description:Urinary extracellular vesicles (uEVs) have shown potential as non-invasive biomarkers for various cancers. However, research on the relationship between uEVs levels and cargo changes after breast cancer surgery remains limited. Therefore, we investigated changes in uEVs levels and proteomes in patients with breast cancer (BC) pre- and post-surgery.
2026-02-24 | PXD061107 | JPOST Repository
Project description:The goal of the RNA-sequencing experiment was to identify differentially expressed genes, ontologies, and pathways based on cell cycle traverse rate (CCTR) in pre-treatment malignant samples from patients with primary operable invasive triple-negative breast cancer (TNBC). TNBC patients belonged to the well-characterized Nottingham Primary Breast Carcinoma series, the database of which was prospectively maintained for another study, although its design accommodates the present retrospective analysis. Most TNBCs exhibited high Nottingham grade and about half of patients exhibited positive lymph nodes. All patients received chemotherapy with cyclophosphamide-methotrexate-5-fluoruracil after surgery (radical mastectomy or breast-conserving surgery). Stained slides used for quantitation of Ki67 index (KI) and mitotic index (MI) were independently scored by two pathologists blinded to clinical annotation, and the scores were averaged. Cell cycle traverse rate (CCTR) was defined as the ratio of the percentage of mitotic cells to the percentage of Ki67-positive cells in full-face formalin-fixed paraffin-embedded sections from primary tumors. To estimate percentages of mitotic cells for each sample, the average mitotic counts for each mitotic score category were first determined, followed by a conversion into percentage after accounting for sample cellularity. Separate slides from formalin-fixed paraffin-embedded malignant samples were used for RNA-sequencing based on the availability of sufficient tissue for analysis. Only tissue from pre-marked tumor areas in these slides were used for RNA-sequencing. RNA was extracted from deparaffinized tissue and first- and second-strand synthesis were performed using commercial kits. Pair-read sequencing was performed using the Illumina HiSeq2500 instrument. The Human Genome Assembly GRCh38.P10 was used as the reference genome for mapping sequence reads. Transcript expression was quantified using Salmon. Differentially expressed genes, ontologies, and pathways were determined based on mean CCTR as well as the optimal CCTR to predict breast cancer-specific survival.
2023-02-20 | E-MTAB-6603 | biostudies-arrayexpress
Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.
2014-07-01 | GSE58792 | GEO
Project description:Single-ventricle defects are palliatively corrected using the Glenn and Fontan procedures that provide lifesaving relief but lead to early mortality rates and poor prognosis post-operatively. The pathophysiology of these complications is diverse, and there are no clear predictors for these outcomes. As such, we aimed to identify novel biomarkers for single-ventricle associated outcomes through the characterization of the serum transcriptome and small extracellular vesicles (sEVs). We report on molecular responses in serum and sEVs pre-operatively and post-operatively in patients undergoing either Glenn or Fontan operations. We found that transcriptomes of serum RNA and sEV RNA are distinctly different, whereas differences between the Fontan and Glenn transcriptomes did not show any significant changes. An in vitro wound healing assay further confirmed that post-operative sEVs have higher angiogenic potential. Moreover, we used a partial-least square regression model to identify 100 RNAs and 50 microRNAs that are involved in angiogenesis-related pathways and accurately predict our wound healing results and compared them with our previously published models of ovine Fontan surgery. Lastly, an EV-origin analysis showed decreased secretion of sEV from cardiac tissue in post-operative samples and increased secretion of sEVs from stomach and nervous tissue. Overall, this study provided evidence that the circulating sEVs transcriptome are potent biomarkers and demonstrated the role of sEVs as a possible mediator for formation of veno-venous collaterals.
2024-12-20 | GSE269879 | GEO