Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profile in relapsed or metastatic HNSCC patients treated with cetuximab and platinum therapy

ABSTRACT: First line chemotherapy with platinum and cetuximab is usually offered to RM-HNSCC pts. In the Extreme trial a median progression free survival (PFS) time of 5.6 months was reported. However, a small fraction of pts achieves a prolonged PFS (> than 12 months). Till now, no recognized predictive biological factor has been identified. A group of 14 cases treated with a first line platinum and cetuximab with a PFS exceeding 12 months (long PFS) and a group of 26 pts with a PFS less than 5.6 months (short PFS) were selected. The 2 groups were well balanced in regard to recognized prognostic factors (performance status, weight loss, prior radiotherapy, tumor grade, site of primary tumor, residual disease at primary tumor site). Tumor specimens of the recurrence or, if not available, of the primary tumor were collected. In order to identify molecular profiles deregulated between the 2 groups, a gene expression microarray analysis was performed using the Whole-Genome DASL assay and HumanHT-12_v4 BeadArray chips (lllumina). Gender: male=0; female=1. Age: years at diagnosis Site of primary: oral cavity=0; oropharynx=1; hypopharynx=2; larynx=3. Stage of T at first diagnosis according to AJCC 8th edition Grading according to WHO: well differentiated=1; moderately differentiated=2; scarcely differentiated=3. Radiotherapy (RT) prior to recurrence: No=0; Yes=1. Progression Free Survival (PFS): Long (>12 months); Short(<5 months).

ORGANISM(S): Homo sapiens

SUBMITTER: Loris De Cecco

PROVIDER: E-GEOD-65021 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Functional Genomics Uncover the Biology behind the Responsiveness of Head and Neck Squamous Cell Cancer Patients to Cetuximab.

Bossi Paolo P Bergamini Cristiana C Siano Marco M Cossu Rocca Maria M Sponghini Andrea P AP Favales Federica F Giannoccaro Marco M Marchesi Edoardo E Cortelazzi Barbara B Perrone Federica F Pilotti Silvana S Locati Laura D LD Licitra Lisa L Canevari Silvana S De Cecco Loris L

Clinical cancer research : an official journal of the American Association for Cancer Research 20160226 15

<h4>Purpose</h4>To identify the tumor portrait of the minority of head and neck squamous cell carcinoma (HNSCC) patients with recurrent-metastatic (RM) disease who upon treatment with platinum-based chemotherapy plus cetuximab present a long-lasting response.<h4>Experimental design</h4>The gene expression of pretreatment samples from 40 HNSCC-RM patients, divided in two groups [14 long-progression-free survival (PFS) and 26 short-PFS (median = 19 and 3 months, respectively)], was associated with ...[more]

PMID: 26920888

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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

Gene expression profile in relapsed or metastatic HNSCC patients treated with cetuximab and platinum therapy

Publications

Functional Genomics Uncover the Biology behind the Responsiveness of Head and Neck Squamous Cell Cancer Patients to Cetuximab.

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