Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA267689 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumor growth reduction induced by anthracycline-based chemotherapy is largely determined by an anticancer immune response that is ignited by the presentation of dead-cell antigens by intratumoral dendritic cells. In an unbiased screen designed to identify cancer therapy-relevant single nucleotide polymorphisms in genes affecting the interaction between dying tumor cells and immune cells, we identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast cancer patients receiving adjuvant chemotherapy. In mice, the therapeutic effects of anthracyclines were abrogated when the immune system was rendered deficient for FPR1 or when tumor cells lacked the FPR1 ligand Annexin A1 (ANXA1). Defective anticancer immune responses from FPR1 knockout mice could be attributed to the failure of dendritic cells to approach dying tumor cells and hence to present tumor cell antigens to T lymphocytes. Experiments performed in a microfluidic device confirmed the obligatory contribution of ANXA1 and FPR1 to the induction of stable conjugates between dying tumor cells and human or murine leukocytes. Altogether, these results underscore the functional and clinical importance of FPR1 in determining chemotherapy-relevant anticancer immune responses.
2016-04-04 | GSE63410 | GEO
Project description:Tumor growth reduction induced by anthracycline-based chemotherapy is largely determined by an anticancer immune response that is ignited by the presentation of dead-cell antigens by intratumoral dendritic cells. In an unbiased screen designed to identify cancer therapy-relevant single nucleotide polymorphisms in genes affecting the interaction between dying tumor cells and immune cells, we identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast cancer patients receiving adjuvant chemotherapy. In mice, the therapeutic effects of anthracyclines were abrogated when the immune system was rendered deficient for FPR1 or when tumor cells lacked the FPR1 ligand Annexin A1 (ANXA1). Defective anticancer immune responses from FPR1 knockout mice could be attributed to the failure of dendritic cells to approach dying tumor cells and hence to present tumor cell antigens to T lymphocytes. Experiments performed in a microfluidic device confirmed the obligatory contribution of ANXA1 and FPR1 to the induction of stable conjugates between dying tumor cells and human or murine leukocytes. Altogether, these results underscore the functional and clinical importance of FPR1 in determining chemotherapy-relevant anticancer immune responses. When the surface of tumor reached 25-45 mm2 after subcutaneous tumor cell innoculation, mice received 2.9 mg/Kg intratumoral doxorubicin (DX) (in 50 μL PBS). Two days after treatment, tumor samples were harvested, rinsed briefly with cold PBS and immediately preserved in RNAlater RNA Stabilization Reagent (Qiagen) overnight at 4°C. Samples were then snap-frozen in liquid nitrogen and stored at -80°C before RNA isolation.
2016-04-04 | E-GEOD-63410 | biostudies-arrayexpress
Project description:Formyl-Peptide Receptor 2 activating probiotic Lactobacilli
| PRJNA1107177 | ENA
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant validation cohort of 198 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
2011-05-11 | E-GEOD-25065 | biostudies-arrayexpress
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant study of 310 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
2011-05-11 | E-GEOD-25055 | biostudies-arrayexpress
Project description:Daunorubicin and doxorubicin, two anthracycline polyketides produced by Streptomyces peucetius, are potent anticancer agents that are widely used in chemotherapy, despite severe side effects. Recent advances have highlighted the potential of producing improved derivatives with reduced side effects by incorporating L-rhodosamine, the N,N-dimethyl analogue of the native amino sugar moiety.
2024-01-18 | PXD048604 | Pride
Project description:Reliable clinical tests for predicting cancer chemotherapy response are not available and individual markers failed to correctly predict resistance against anticancer agents. We hypothesized that gene expression patterns attributable to chemotherapy-resistant cells can be used as a classification tool for chemoresistance and provide novel candidate genes involved in anthracycline resistance mechanisms. We contrasted the expression profiles of 4 different human tumor cell lines of gastric, pancreatic, colon and breast origin and of their counterparts resistant to the topoisomerase inhibitors daunorubicin or doxorubicin. We also profiled the sensitive parental cells treated with doxorubicin for 24h. We interrogated Affymetrix HGU133A and U95A arrays independently. We applied two independent methods for data normalization and used Prediction Analysis of Microarrays (PAM) for feature selection. In addition, we established data sets related to drug resistance by using a “virtual array” composed of features represented on both types of oligonucleotide arrays. We identified 71 candidate genes associated with doxorubicine/daunorubicine resistance. To validate the microarray data, we also analyzed the expression of 12 selected genes by quantitative RT-PCR or immunocytochemistry, respectively. While the comparison of drug-sensitive versus drug-resistant cells yields candidates associated with drug resistance, the 24h treatment of sensitive parental cells produced a distinct transcriptional profile related to short-term drug effects. Keywords: superSeries This reference Series links data in the following related Series: GSE3926 Anthracycline treatment and resistance in four human cancer cell lines (HGU133A) GSE3927 Anthracycline resistance in four human cancer cell lines (HGU95A)
2010-04-14 | E-GEOD-3929 | biostudies-arrayexpress
Project description:Although chemotherapy induces complete remission in the majority of acute myeloid leukemia (AML) patients, many face a relapse. This relapse is caused by survival of chemotherapy-resistant leukemia (stem) cells, called measurable residual disease (MRD). Here, we demonstrate that the anthracycline doxorubicin epigenetically reprograms leukemia cells by inducing tri-methylation of histone 3 lysine 27 (H3K27) and H3K4. Moreover, within a doxorubicin-sensitive leukemia cell population, we identified a subpopulation of reversible anthracycline-tolerant cells (ATCs) with leukemic stem cell (LSC) features lacking upregulation of doxorubicin-induced H3K27me3 or H3K4me3. These ATCs have a distinct transcriptional landscape than the leukemia bulk and could be eradicated by inhibition of KDM6. In primary AML, reprogramming the transcriptional state by targeting KDM6 reduced MRD load and survival of LSCs residing within MRD, and enhanced the response to chemotherapy in vivo. Together, our results reveal plasticity of anthracycline resistance in AML cells and highlight the potential of transcriptional reprogramming by epigenetic-based therapeutics to target chemotherapy-resistant AML cells.
2022-08-15 | GSE210916 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE25055: Discovery cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer GSE25065: Validation cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer Refer to individual Series
2011-05-11 | E-GEOD-25066 | biostudies-arrayexpress