Response prediction to neoadjuvant chemotherapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29561 | GEO | 2012/10/26
SECONDARY ACCESSION(S): PRJNA141331
REPOSITORIES: GEO
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Project description:We investigated whether we could identify gene expression profiles in initial core biopsies of breast cancer samples that would permit to a) predict a clinically meaningful response to Epi/Doc in terms of tumor size reduction, b) predict a profound reduction in intratumoral Ki67 protein expression, and c) predict an in vitro response to Epi/Doc in the ATP-TCA. 22 Samples from breast cancer patients with corresponding treatment response indicators
2012-10-26 | E-GEOD-29561 | biostudies-arrayexpress
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Keywords: Study about estrogen response of osteoclast-specific estrogen receptor alpha mice
2007-06-01 | GSE7798 | GEO
Project description: Not available
| S-ECPF-GEOD-29561 | biostudies-other
Project description:The feasibility of longitudinal metastatic biopsies for gene expression profiling in breast cancer is unexplored. Dynamic changes in gene expression can potentially predict efficacy of targeted cancer drugs. Patients enrolled in a phase III trial of metastatic breast cancer with sunitinib combined with docetaxel (SU+DOC) versus docetaxel alone (DOC) were offered to participate in a translational substudy comprising longitudinal fine needle aspiration biopsies (FNAB) and positron emission imaging before (T1) and two weeks after start of treatment (T2). Aspirated tumor material was used for microarray analysis, and treatment-induced changes (T2 versus T1) in gene expression and standardized uptake values were investigated. Twenty-one patients were included in the docetaxel ± sunitinib trial at Karolinska and 18 of them agreed to participate in the substudy. Of the 18 women enrolled, 8 were randomly assigned to SU+DOC and 10 to DOC. Metastatic FNAB were carried out in 17 of the 18 patients at both time points with no complications reported. Representative tumor material, sufficient for RNA extraction was obtained in 15 patients at T1 and 14 patients at T2. Matched samples both at T1 and T2 were obtained for 14 subjects, 7 in each arm. The main objective was to determine whether gene expression profiling is feasible using sequential, intra-patient FNAB. Secondary objectives were to identify potential biomarkers of early response by gene expression and/or functional imaging and to explore drug action in vivo by changes in gene expression.
2015-04-14 | GSE54323 | GEO
Project description:The feasibility of longitudinal metastatic biopsies for gene expression profiling in breast cancer is unexplored. Dynamic changes in gene expression can potentially predict efficacy of targeted cancer drugs. Patients enrolled in a phase III trial of metastatic breast cancer with sunitinib combined with docetaxel (SU+DOC) versus docetaxel alone (DOC) were offered to participate in a translational substudy comprising longitudinal fine needle aspiration biopsies (FNAB) and positron emission imaging before (T1) and two weeks after start of treatment (T2). Aspirated tumor material was used for microarray analysis, and treatment-induced changes (T2 versus T1) in gene expression and standardized uptake values were investigated. Twenty-one patients were included in the docetaxel ± sunitinib trial at Karolinska and 18 of them agreed to participate in the substudy. Of the 18 women enrolled, 8 were randomly assigned to SU+DOC and 10 to DOC. Metastatic FNAB were carried out in 17 of the 18 patients at both time points with no complications reported. Representative tumor material, sufficient for RNA extraction was obtained in 15 patients at T1 and 14 patients at T2. Matched samples both at T1 and T2 were obtained for 14 subjects, 7 in each arm. The main objective was to determine whether gene expression profiling is feasible using sequential, intra-patient FNAB. Secondary objectives were to identify potential biomarkers of early response by gene expression and/or functional imaging and to explore drug action in vivo by changes in gene expression. A Karolinska substudy of the docetaxel ± sunitinib phase III clinical trial utilising sequential metastatic fine needle aspiration biopsies (FNAB) and 18-F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT). In brief, the randomized docetaxel ± sunitinib trial compared sunitinib combined with docetaxel (SU+DOC) versus docetaxel alone (DOC), as first line therapy in patients with HER2 negative metastatic breast cancer. Patients in the exploratory substudy were subjected to baseline FDG PET/CT assessment, followed by FNAB of one tumor lesion prior to start of treatment (Time point T1). FDG PET/CT and FNAB were repeated at Day 14 ± 1 (Time point T2) when sunitinib has achieved steady state.
2015-04-14 | E-GEOD-54323 | biostudies-arrayexpress
Project description:Response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer is linked to long-term patient survival. However, response to NAC is highly variable and cannot reliably be predicted by clinical or other current methods. This study aims to address this problem by utilising the stable, yet dynamic marker known as DNA methylation. By defining the methylation differences at diagnosis in patients that achieve a pathological complete remission against those that do not respond, we can identify a marker that can potentially predict chemotherapy response and help further personalise the chemotherapy decision making in the clinic.
2021-12-17 | GSE184159 | GEO
Project description:Genome wide gene expression analysis of mRNA siolated from whole heart tissue from wild type and cardiomyocyte selective MR null mice. The role of mineralocorticoid receptors (MR) in specific cell types of the myocardium in cardiac remodeling remains unknown. We investigated MR in cardiomyocytes in DOC/salt-induced cardiac pathology. Cardiomyocyte MR-null mice (CM-MRKO) and control mice (WT) were given DOC/salt and cardiac responses were examined at 8 days and 8 weeks. Cardiac function in untreated mice wild type and CM-MRKO mice was determined by Langendorf and showed no differences. At 8 days CM-MRKO showed equivalent monocyte/macrophage recruitment to wild type mice in response to DOC/salt treatment. Profibrotic markers were significantly reduced in CM-MRKO hearts at base line and in response to DOC/salt. In contrast, at 8 weeks CM-MRKO mice showed no DOC/salt-induced increase in inflammatory cell infiltrate, fibrosis or systolic blood pressure (SBP). Similarly, DOC/salt-mediated increases in proinflammatory and profibrotic gene expression were not detected in CM-MRKO mice. Although mRNA levels for fibronectin and collagen III were similar for each genotype, this was not translated into protein expression. Interestingly, untreated CM-MRKO mice showed increased mRNA and protein for decorin and a further increase with DOC/salt. Together, these data suggest a direct role for cardiomyocyte MR in DOC/salt-induced tissue remodelling and SBP regulation. Moreover, a specific profibrotic pathway is dysregulated in CM-MRKO mice, suggesting a potential mechanism for the cardioprotective effects of selective MR deletion in cardiomyocytes.
2013-06-30 | GSE38869 | GEO
Project description:We used the mouse pathogen Citrobacter rodentium to model gut infections. Following oral inoculation C. rodentium resides in the caecum for the first 3 days, before it infects the colon on the 4th day. Here we show that while the host is unresponsive to the infection on day 3, there is an abrupt reprogramming of the cellular composition of the crypt, involving depletion of goblet and deep crypt secretory cells, as well as metabolism (e.g. simultaneous up-regulation of cholesterol biogenesis, import and efflux), DNA damage repair and proliferation, which correlated with Ki67 staining, on day 4. Reduction in the abundance of proteins involved in the TCA cycle and oxidative phosphorylation, leading to oxygenation of the gut, coincided with instant expansion of mucosal-associated Enterobacteriaceae. These results show that sensing a small number of pathogenic bacteria triggers immediate intrinsic changes to the epithelium physiology and the microbiota, which parallel innate gut immune responses.
2019-03-05 | PXD012031 | Pride
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Experiment Overall Design: Wild type and osteoclast-specific Estrogen Receptor alpha knock-out mice were ovariectomized. The number of both genotypes of mice was eight. The mice of each genotypes were divided to vehicle control and estrogen treated group. Four hours after chemical treatment, the distal 5 mm of the left femurs were harvested after sacrificing by cervical dislocation and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling. Therefore, this experiment consists of four groups with four replicates per group.
2008-06-15 | E-GEOD-7798 | biostudies-arrayexpress
Project description:The function of cvpA, a bacterial gene predicted to encode an inner membrane protein, is largely unknown. Early studies in E. coli linked cvpA to Colicin V secretion and recent work revealed that it is required for robust intestinal colonization by diverse enteric pathogens. In enterohemorrhagic E. coli (EHEC), cvpA is required for resistance to the bile salt deoxycholate (DOC). Here, we carried out genome-scale transposon-insertion mutagenesis and spontaneous suppressor analysis to uncover cvpA’s genetic interactions and identify common pathways that rescue the sensitivity of a ∆cvpA EHEC mutant to DOC. These screens demonstrated that mutations predicted to activate the σE-mediated extracytoplasmic stress response bypass the ∆cvpA mutant’s susceptibility to DOC. Consistent with this idea, we found that deletions in rseA and msbB and direct overexpression of rpoE restored DOC resistance to the ∆cvpA mutant. Analysis of the distribution of CvpA homologs revealed that this inner membrane protein is conserved across diverse bacterial phyla, in both enteric and non-enteric bacteria that are not exposed to bile. Together, our findings suggest that CvpA plays a role in cell envelope homeostasis in response to DOC and similar stress stimuli in diverse bacteria.
2020-12-01 | GSE162346 | GEO