MRNA expression profile of regulatory neutrophil induced by sodiumtaurodeoxycholate
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE49593 | GEO | 2022/06/30
REPOSITORIES: GEO
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2014-12-31 | GSE56241 | GEO
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Project description:We have reported that intra-tumoral treatment with 1V270, a phospholipid-conjugated TLR7 agonist,induces local expansion an systemic dispersion of oligoclonal tumor-specific T cells by TCR repertoire analysis using next generation RNAseq methodology. Here, we examined whether systemic 1V270 therapy also induced oligoclonal expansion of tumor-specific T cells. Two groups of BALB/c mice (n=4/group) were i.p. treated with 1V270,a phospholipid-conjugated TLR7 agonist. One cohort of mice was i.v. injected with 4T1-GLF cells (2×104) on day 0. Another cohort did not receive i.v. tumor injection (no tumor-exposed mice). 4T1 cells were orthotopically inoculated on day 21. To examine clonal specificity of tumor-specific T cells, CD8+ cells were isolated from the spleens and the tumor infiltrating lymphocytes of secondarily challenged tumors after initial 1V270 therapy. The TCR repertoires were assessed by next generation RNA sequencing of both TCRαand TCR β genes.
2018-07-31 | E-MTAB-6566 | biostudies-arrayexpress
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2022-09-16 | GSE150470 | GEO
Project description:<p>The SUCCESS-A Study (<a href="http://www.success-studie.de">http://www.success-studie.de</a>) is a randomized Phase III study of response to treatment of early primary breast cancer with adjuvant therapy after surgical resection. The primary outcome is disease-free survival and secondary outcomes are overall survival and toxicity. The study design includes comparison of two pairs of treatment regimes performed in sequence. The first randomization contrasts treatment with and without Gemcitabine (3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC)-chemotherapy, followed by 3 cycles of Docetaxel(D)-chemotherapy versus 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC), followed by 3 cycles of Gemcitabine-Docetaxel(DG)-chemotherapy). The second randomization contrasts treatment with Zoledronate for two versus five years. Patients were recruited from 2005 to 2007 and a total of 3754 patients were included from 250 study sites across Germany. Genome-wide SNP microarray data and phenotype outcomes for the first phase of the study (treatment with and without Gemcitabine) are included in the GARNET (Genomics and Randomized Trials Network) pharmacogenomic study in this dbGaP submission. (The Zoledronate treatments are still underway).</p> <p>SUCCESS-A is a an open-label, multicenter, 2x2 factorial design, randomized controlled, Phase III study comparing the disease free survival after randomization in patients treated with 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC)-chemotherapy, followed by 3 cycles of Docetaxel(D)-chemotherapy versus 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC), followed by 3 cycles of Gemcitabine-Docetaxel(DG)-chemotherapy, and to compare the disease free survival after randomization in patients treated with 2 years of Zoledronate versus 5 years of Zoledronate in patients with early primary breast cancer. Patients were required to have histopathological proof of axillary lymph node metastases (pN1-3) or high risk node negative, defined as: pT>2 or histopathological grade 3, or age , ≤ 35 or negative hormone receptor, but were not allowed to have evidence of distant disease. Patients were entered into the study no later than 6 weeks after complete resection of the primary tumor. No antineoplastic treatment other than surgical treatment, the defined cytotoxic and endocrine treatment, and radiotherapy was allowed prior to study entry and during the course of the study. After surgery, leading to complete resection of the invasive and intraductal components of the primary tumor, patients were randomized to one of the following two treatments for the first phase of the project (which is included in this GARNET pharmacogenomics study):</p> <p><b>AA</b>: 3 cycles of 5-Fluorouracil 500 mg/m² i.v. body surface area and Epirubicin 100 mg/m² i.v. and Cyclophosphamide 500 mg/m² i.v., (FEC100), each administered on day 1, repeated on day 22, subsequently followed by 3 cycles of Docetaxel 75 mg/m² body surface area i.v. (D), and Gemcitabine 1000 mg/m² i.v. (30 min infusion) (G), administered on day 1, followed by Gemcitabine 1000 mg/m² i.v. (30 min infusion) on day 8, repeated on day22</p> <p><b>AB</b>: 3 cycles of 5-Fluorouracil 500 mg/m² i.v. body surface area and Epirubicin 100 mg/m² i.v. and Cyclophosphamide 500 mg/m² i.v., (FEC100), each administered on day 1, repeated on day 22, subsequently followed by 3 cycles of Docetaxel 100 mg/m² body surface area i.v. (D), administered on day 1, repeated on day 22</p> <p>A second randomization was made for assigning patients to one of the following two subsequent treatments for the second phase of the project (NOT included in the pharmacogenetic study in this dbGaP submission):</p> <p><b>BA</b>: Zoledronic acid 4 mg i.v., every 3 months for the duration of two years, subsequently followed by zoledronic acid 4 mg i.v., every 6 months for the duration of additional three years</p> <p><b>BB</b>: Zoledronic acid 4 mg i.v., every 3 months for the duration of two years</p> <p>Patients with positive hormone receptor status (≥10% positively stained cells for estrogen and/or progesterone) of the primary tumor were recommended to receive Tamoxifen treatment 20 mg p.o. per day for 2 years, after the end of chemotherapy . Subsequent to chemotherapy, postmenopausal patients with positive hormone receptor status were recommended to be treated with Anastrozole (Arimidex®) 1 mg p.o. for additional 3 years, premenopausal patients will continue Tamoxifen treatment for those additional 3 years. In addition to tamoxifen, all patients with positive hormone receptor status of the primary tumor and under the age of 40 or restart of menstrual bleeding within 6 months after the completion of cytostatic treatment or with premenopausal hormone levels as defined below were recommended to receive Goserelin (Zoladex®) 3.6 mg subcutaneously every 4 weeks over a period of 2 years following chemotherapy. Premenopausal endocrine status will be assumed, if the following serum levels are met: LH < 20 mIE/ml, FSH < 20 mIE/ml and E2 > 20 pg/ml. Endocrine therapy will start after the end of chemotherapy.</p> <p>All patients with breast conserving therapy or more than 3 axillary lymph node metastases or in the following cases after mastectomy will receive adjuvant radiotherapy: T3/T4-carcinoma, T2-carcinoma > 3 cm, multicentric tumor growth, lymphangiosis carcinomatosa or vessel involvement, involvement of the pectoralis fascia or a safety margin < 5 mm. Radiotherapy was usually performed after the chemotherapy and parallel to the beginning of the zoledronic acid therapy.</p> <p>Initially, DNA was extracted for performing SNP microarray assays using blood collected at baseline prior to the first randomization. However, the first set of SNP microarray results indicated a quality problem with approximately 50% of the DNA samples. A majority of the problematic samples were replaced with DNA extracted from redrawn blood. The remaining problematic samples were 'restored' using an Illumina FFPE Restoration procedure. A total of 3322 subjects (1638 from arm AA and 1684 from arm AB) were successfully genotyped. Among those, 1771 were from original blood samples, 1092 from redrawn blood samples and 459 from restored blood samples.</p> <p>The SUCCESS-A study is part of the Genomics and Randomized Trials Network (GARNET, <a href="http://www.garnetstudy.org">http://www.garnetstudy.org</a>) funded by the National Human Genome Research Institute (NHGRI). The overarching goal is to identify novel genetic factors that contribute to disease-free survival for breast cancer patients using different forms of chemotherapy through large-scale genome-wide association studies of treatment response in randomized clinical trials. The study was conducted at the University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Germany. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were performed at the GARNET Coordinating Center at the University of Washington.</p>
| phs000547 | dbGaP
Project description:We compared splenic Va14i NKT cells from C57BL/6 control mice and from mice injected 4 weeks earlier intravenously with 4ug/mouse of the iNKT cell antigen alpha-galactosylceramide (aGalCer). These mice were either left unstimulated or were stimulated with 1ug/mouse aGalCer i.v.. All mice were female and 8 weeks of age at the beginning of the experiment. Va14i NKT cells were enriched via magnetic selection and cell sorted for TCRb+ CD1d/aGalCer-tetramer+. Total RNA were prepared using a Qiagen RNeasy mini kit. IVT probe generation and hybridization to Affymetrix Mouse Genome 430 2.0 arrays was carried out by the Veterans Medical Research Foundation GeneChipTM Microarray located at UCSD. Group 1 (Ctr_unstim) = iNKT cells from C57BL/6 control mice and left unstimulated / Group 2 (Ctr_stim) = iNKT cells from C57BL/6 control mice and injected 1h before purification with 1ug aGalCer i.v. / Group 3 (Pre_unstim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and left unstimulated / Group 4 (Pre_stim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and injected 1h before purification with 1ug aGalCer i.v. / Sample were prepared in duplicates in two independent experiments.
2014-07-25 | E-GEOD-47959 | biostudies-arrayexpress
Project description:Adoptive transfer of CD4+ T cells (TRP-1 CD4+ T cells) specific for tyrp-1 (tyrosinase-related protein 1) eradicate established tumors (melanoma) in lymphopenic RAG-/- hosts. In vitro differentiated CD8+ T cells have been the primary focus of immunotherapy of cancer with little focus on CD4+ T cells. Immunotherapy involving in vitro differentiated T cells given after lymphodepleting regimens significantly augments antitumor immunity in animals and human patients with cancer. However, the mechanisms by which lymphopenia augments adoptive cell therapy and the means of properly differentiating T cells in vitro are still emerging. We demonstrate that naïve tumor/self-specific CD4+ T cells naturally differentiated into T helper type 1 (Th1) cytotoxic T cells in vivo and caused the regression of established tumors and depigmentation in lymphopenic hosts. Therapy was independent of vaccination, exogenous cytokine support, CD8+-, B-, NK and NK-T cells. Proper activation of CD4+ T cells in vivo was important for tumor clearance as naïve tumor-specific CD4+ T cells could not completely treat tumor in lymphopenic common gamma chain-deficient (gc-/-) hosts. gc signaling in the tumor-bearing host was important for survival and proper differentiation of adoptively transferred tumor-specific CD4+ T cells. Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4+ T cells. 2 x 10^5 sorted TRP-1 CD4+ T cells were transferred i.v. into tumor-bearing RAG-/- hosts on day 7-10 after tumor challenge, and ~1 x 10^6 CD4+ T cells were isolated 1 week later by flow sorting from pooled lymph nodes (LN) or spleens. Dye-swaps were performed.
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