Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MicroRNA alterations associated to early relapse in advanced stage ovarian cancer patients (validation set)

ABSTRACT: A set of 45 surgical specimens has been profiled for miRNA expression to validate miRNA alterations associated to early relapse in advanced stage ovarian cancer patients. Fresh frozen samples were collected from a series of consecutive patients with high-grade advanced stage ovarian cancer who underwent primary surgery at INT-Milan. After surgery all patients received postoperative platinum-based chemotherapy. All patients signed an Institutional Review Board approved consent for bio-banking, clinical data collection and molecular analysis. Clinical codes: Histotype: according to WHO classification guidelines Stage: according to International Federation of Gynecological and Obstetrics (FIGO) guidelines Grading: according to WHO classification guidelines Debulking: NED: not evident disease; mRD: minimal residual disease; GRD: gross residual disease Therapy code: P: Platinum without taxanes; PT: Platinum/paclitaxel

ORGANISM(S): Homo sapiens

SUBMITTER: Loris De Cecco

PROVIDER: E-GEOD-67819 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of a chrXq27.3 microRNA cluster associated with early relapse in advanced stage ovarian cancer patients.

Bagnoli Marina M De Cecco Loris L Granata Anna A Nicoletti Roberta R Marchesi Edoardo E Alberti Paola P Valeri Barbara B Libra Massimo M Barbareschi Mattia M Raspagliesi Francesco F Mezzanzanica Delia D Canevari Silvana S

Oncotarget 20111201 12

A major challenge in advanced-stage epithelial ovarian cancer (EOC) is prediction of chemoresistant relapse. Our aim was to identify a microRNA (miRNA) signature associated with early relapse in advanced-stage EOC patients. miRNA expression was assessed by microarray profiling in training (n = 55) and test (n = 30) sets selected on the basis of time to relapse (TTR), followed by internal quantitative reverse transcriptase-PCR validation on a set of 45 consecutive cases unselected for clinical re ...[more]

PMID: 22246208

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Project description:Disease relapse and resistance to chemotherapy represent challenging issues in a subset of Hodgkin Lymphoma (HL) patients. Activity and mechanism(s) of action of a novel PI3K/ERK dual inhibitor AEZS-136 (Ãterna Zentaris GmbH, Germany, EU) were examined in L-540, SUP-HD1, KM-H2 and L-428 cell lines. Despite exposure to AEZS-136 induced a significant cell growth inhibition (range, 30-80%), levels of caspase-independent cell death and mitochondrial dysfunction, were only observed in L-540 (62 Â±9 vs 14 Â±3%, P â¤.0001) and SUP-HD1 (46 Â±2% vs 15 Â±2%, P â¤.0001) cells. Gene expression profiling indicated that the effects of AEZS-136 treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to AEZS-136 resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented AEZS-136-induced ROS production, mitochondrial injury, activation of JNK and cell death. Knockdown experiments identified the immediate early response 3 (IER3) as a key signaling molecule that mediates AEZS-136-resistance to oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 40-70% reduction in tumor burden (P < 0.0001) and a 10-fold increase in tumor necrosis in AEZS-136-treated animals compared to control mice. These data support further clinical evaluation of AEZS-136 in refractory/relapsed HL. The Hodgkin lymphoma cell lines were obtained from the DSMZ (Braunschweig, Germany, EU). Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 20% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37Â°C in a water-saturated atmosphere of 5% CO2 in air. 4x106 HL cells were seeded in 75 cm2 flask and, after 24 hrs, cells were treated with 10 ÂµM AEZS-136 (Aeterna Zentaris, Frankfurt, Germany, EU) in culture medium for 24 hours. At the end of treatment, cells were collected and RNA extracted.

Dataset Information

MicroRNA alterations associated to early relapse in advanced stage ovarian cancer patients (validation set)

Publications

Identification of a chrXq27.3 microRNA cluster associated with early relapse in advanced stage ovarian cancer patients.

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