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RANK-Fc treatment in MMTV-PyMT late carcinoma

ABSTRACT: Transcriptional profile of MMTV-PyMT late carcinomas after adjuvant or neoadjuvant treatment with RANK-Fc (receptor activator of NF-kB) cells isolated from one single MMTV-PyMT carcinoma were orthotopically injected in syngeneic WT mice, which were randomized 1:1 for neoadjuvant RANK-Fc or mock treatment (passage 1) for 4 weeks. Cells isolated from both treatment arms were pooled and injected into the fat pad of FvB recipients (passage 2) in limiting dilutions (mimicking occult disease) and again randomized 1:1 for additional RANK-Fc (adjuvant) or mock treatment

ORGANISM(S): Mus musculus

PROVIDER: GSE66085 | GEO | 2016/12/19

SECONDARY ACCESSION(S): PRJNA275855

REPOSITORIES: GEO

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Mus musculus

Project description:RANK-Fc treatment in MMTV-PyMT late carcinoma

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Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma

Project description:Glioblastoma is the most common primary malignant brain tumor in adults and associated with poor survival. Standard-of-care chemotherapy and radiation confer a median overall survival of under two years. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical PD-1 blockade alone (hazard ratio = 0.39; P = 0.04, log-rank test). Neoadjuvant PD-1 blockade was associated with upregulation of T cell and interferon-γ-related genes, but downregulation of cell cycle related genes within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 (PD-L1) in the tumor microenvironment was observed more frequently in the neoadjuvant group than in tumors obtained from patients treated only in the adjuvant setting. Similarly, neoadjuvant pembrolizumab was associated with clonal T cell expansion and the overlap of T cell receptors between tumor and blood, decreased PD-1 expression in T cells and a decreasing peripheral monocytic population. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances the local and systemic anti-tumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor. This trial was registered with ClinicalTrials.gov under the identifier NCT02852655 (https://clinicaltrials.gov/ct2/show/NCT02852655).

2018-12-05 | GSE121810 | GEO

CD45- sorted tumor cells from RANK+/+ and RANK-/- MMTV_PYMT late carcinomas

Project description:Transcriptional profile of either RANK+/+ or RANK-/- MMTV-PyMT late carcinomas, orthotopically injected in syngeneic RANK+/+ mice. Once host mice developed tumors, CD45- tumor cells were sorted by flow cytometry in order to compare changes on tumor gene expression caused by the absence of RANK protein.

2020-10-06 | GSE119464 | GEO

RANKL-RANK activation in mmtv-Pymt primary tumor cultures

Project description:MMTV-PyMT late carcinomas, orthotopically injected in syngeneic RANK+/+ mice were digested until single cells and cultured over Matrigel in the prescence or abscence of RANKL for 24 hours.

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RANKL-RANK activation in mmtv-Pymt primary tumor cultures

Project description:RANKL-RANK activation in mmtv-Pymt primary tumor cultures

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Effect of Spot14 Loss on Gene Expression Profile of MMTV-PyMT Mouse Tumors

Project description:The objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) loss on the gene expression profiles of tumors from MMTV-Polyomavirus middle-T antigen (PyMT) mice. MMTV-PyMT/S14-heterozygous mice were crossed with S14-heterozygous mice and 1 cm tumors from MMTV-PyMT control (wild-type S14) or MMTV-PyMT/S14-null offspring were profiled using Affymetrix gene arrays. Tumor latency was not different between groups; however, tumors lacking S14 grew significantly slower than control tumors. Loss of S14 also decreased the levels of de novo synthesized fatty acids in mammary tumors. In additional studies, performed on MMTV-Neu mice, we found that S14 overexpression was associated with increased tumor cell proliferation and elevated levels of tumor fatty acids. Gene expression profiling revealed that S14 loss and overexpression in mouse mammary tumors altered pathways associated with proliferation and metabolism. This study provides important information about the role of S14 in mammary tumorigenesis and tumor metabolism. Microarray analysis was performed on 4 mammary tumors from MMTV-PyMT mice and 4 tumors from MMTV-PyMT/S14-null mice.

2014-09-01 | E-GEOD-55886 | biostudies-arrayexpress

Single-cell RNA profiling of mammary gland tumours in MMTV-PyMT mouse model of breast cancer.

Project description:Here, we use single cell sequencing to delineate the heterogeneity of tumours from the genetically engineered MMTV-PyMT mouse model of breast cancer (MMTV-PyMT::K14Cre::Rosa-tdTomato mice).

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Expression data from MMTV-PyMT Induced Tumors

Project description:Loss of E2F transcription factos alters metastatic capacity of MMTV-PyMT tumors. We used microarrays to futher characterize the effects of E2F loss on mammary tumorigenesis in MMTV-PyMT mice.

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Expression data of MMTV-PyMT mice mammary tumor with or without JAM-A

Project description:Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature. Each 3 MMTV-PyMT JAm-A+/+ (JamA+) and 3 MMTV JAM-A-/- (JamA-) mammary tumor were resected at early stages of tumor development for RNA extraction and hybridization on Affymetrix microarrays.

2010-10-01 | E-GEOD-22555 | biostudies-arrayexpress

RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and functionally contributes to increase tumor aggressiveness

Project description:Analyses of genes expression in estrogen receptor negative, RANK positive, breast cancer orthoxenografts after in vivo treatment (4 weeks) with RANKL , RANK-Fc or denosumab.

2023-01-19 | GSE185513 | GEO

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