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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-Longterm]

ABSTRACT: EGFR-inhibition is required for targeted therapies of EGFR high/ERBB2 positive breast cancer. Approximately 30% of human ERBB2 positive breast tumors also express EGFR. Three therapeutics were analyzed in five combinations plus control. Each experiment was performed in three biological replicates. This resulted in 180 samples. A dilution series of control lysated was included as control.

ORGANISM(S): Homo sapiens

SUBMITTER: Ulrike Korf

PROVIDER: E-GEOD-36325 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer

Project description:This SuperSeries is composed of the following subset Series: GSE36324: Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-HCC1954] GSE36325: Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-Longterm] GSE36326: Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-SKBR3] Refer to individual Series

2012-10-22 | E-GEOD-36327 | biostudies-arrayexpress

Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-HCC1954]

Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR. Three targeted therapeutics (erlotinib, pertuzumab, trastuzumab) and two ligands (EGF, HRG) were analyzed in all possible combinations. Each experiment involving inhibition with targeted drugs was performed in three, and measurements without inhibitors were performed in five biological replicates. This resulted in 780 samples. Incubation with therapeutics only and dilution series of control lysated were included as controls.

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Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-SKBR3]

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Targeted inhibition of three human breast cancer cell lines as model systems of ERBB2-positive breast cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-08-22 | E-GEOD-50109 | biostudies-arrayexpress

Reverse phase protein array based protein profiling of breast cancer specimens

Project description:Expression levels of proteins and phosphoproteins, covering major cancer signaling pathways with a special focus on breast cancer biology, were obtained for a series of 109 breast cancer tumor specimens with positive estrogen receptor status. Tumor specimens from patients diagnosed with primary invasive breast carcinoma were collected at the time of surgery between 2008 and 2010 at the Department of Gynecology and Obstetrics / National Center for Tumor Diseases Heidelberg. None of the patients had received neoadjuvant therapy. Institutional Review Board approval was received as ethics vote no. S039/2008 and informed consent was obtained from all patients. Tumor specimens were processed within 20 min after surgery. Samples were stored snap frozen at -80M-BM-0C until further use. Only tumor samples with > 70% tumour cells and positive estrogen receptor status (immunoreactive score M-bM-^IM-% 3) as assessed by routine immunohistochemistry were selected for this study (n = 109). Tumor lysates were printed on a series of nitrocellulose coated glass slides and probed with 128 different primary antibodies directed against proteins and phosphoproteins of interest. Primary antibodies were selected to recognize proteins involved in major cancer signaling pathways with a special focus on breast cancer biology.

2014-02-18 | E-GEOD-47066 | biostudies-arrayexpress

Reverse phase protein array based protein profiling of breast cancer specimens (2)

Project description:Expression levels of proteins and phosphoproteins, covering major cancer signaling pathways with a special focus on breast cancer biology, were obtained for a series of 164 breast cancer tumor specimens with positive estrogen receptor status. Tumor specimens from patients diagnosed with primary invasive breast carcinoma were collected at the time of surgery between 2005 and 2011 and provided by the NCT Tissue Bank Heidelberg as well as by the Department of Gynecology and Obstetrics / National Center for Tumor Diseases Heidelberg. None of the patients had received neoadjuvant therapy.Tumor specimens were processed within 20 min after surgery. Samples were stored snap frozen at -80M-BM-0C until further use. Only tumor samples with > 70% tumour cells and positive estrogen receptor status (immunoreactive score M-bM-^IM-% 3) as assessed by routine immunohistochemistry were selected for this study (n = 164). Tumor lysates were printed on a series of nitrocellulose coated glass slides and probed with with differnt primary antibodies directed against proteins and phosphoproteins of interest. Primary antibodies were selected to recognize proteins involved in major cancer signaling pathways with a special focus on breast cancer biology.

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Dynamic re-wiring of apoptotic signaling networks enhances tumor cell killing by DNA damage

Project description:Crosstalk and complexity within signaling pathways has limited our ability to devise rational strategies for using network biology to treat human disease. This is particularly problematic in cancer where oncogenes that drive or maintain the tumorigenic state alter the normal flow of molecular information within signaling networks that control growth, survival and death. Understanding the architecture of oncogenic signaling pathways, and how these networks are re-wired by ligands or drugs, could provide opportunities for the specific targeting of oncogene-driven tumors. Here we use a systems biology-based approach to explore synergistic therapeutic strategies to optimize the killing of triple negative breast cancer cells, an incompletely understood tumor type with a poor treatment outcome. Using targeted inhibition of oncogenic signaling pathways combined with DNA damaging chemotherapy, we report the surprising finding that time-staggered EGFR inhibition, but not simultaneous co-administration, can dramatically sensitize the apoptotic response of a subset of triple-negative cells to conventional DNA damaging agents. A systematic analysis of the order and timing of inhibitor/genotoxin presentation—using a combination of high-density time-dependent activity measurements of signaling networks, gene expression profiles, cell phenotypic responses, and mathematical modeling—revealed an approach for altering the intrinsic oncogenic state of the cell through dynamic re-wiring of oncogenic signaling pathways. This process converts these cells to a less tumorigenic state that is more susceptible to DNA damage-induced cell death, through re-activation of an extrinsic apoptotic pathway whose function is suppressed in the oncogene-addicted state. Three or 4 replicates of 3 different cell lines at time points 0minutes, 30minutes, 6 hours and 1 day after EGFR inhibition with erlotinib

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SILAC proteomics analysis to discover effect sensors of EGFR inhibition

Project description:Targeted therapies against EGFR show clinical benefit, but resistance to these agents invariably develops. Thus, there is a need for dynamic biomarkers - effect sensors - that reflect treatment with EGFR therapeutics during therapy. Making use of SILAC-labeling we aimed to discover plasma membrane proteins that become differentially expressed after treatment with EGFR inhibitor erlotinib in three erlotinib-sensitive breast cancer cell lines.

2018-10-18 | PXD005985 | Pride

Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-SKBR3]

Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.

2012-10-22 | GSE36326 | GEO

Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-Longterm]

Project description:EGFR-inhibition is required for targeted therapies of EGFR high/ERBB2 positive breast cancer. Approximately 30% of human ERBB2 positive breast tumors also express EGFR.

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