Construction of 12 EST libraries and characterization of a 12,226 EST dataset for chicory (Cichorium intybus) root, leaves and nodules in the context of carbohydrate metabolism investigation

<p>Abstract</p> <p>Background</p> <p>The industrial chicory, <it>Cichorium intybus</it>, is a member of the <it>Asteraceae </it>family that accumulates fructan of the inulin type in its root. Inulin is a low calories sweetener, a texture agent and a health promoting ingredient due to its prebiotic properties. Average inulin chain length is a critical parameter that is genotype and temperature dependent. In the context of the study of carbohydrate metabolism and to get insight into the transcriptome of chicory root and to visualize temporal changes of gene expression during the growing season, we obtained and characterized 10 cDNA libraries from chicory roots regularly sampled in field during a growing season. A leaf and a nodule libraries were also obtained for comparison.</p> <p>Results</p> <p>Approximately 1,000 Expressed Sequence Tags (EST) were obtained from each of twelve cDNA libraries resulting in a 12,226 EST dataset. Clustering of these ESTs returned 1,922 contigs and 4,869 singlets for a total of 6,791 putative unigenes. All ESTs were compared to public sequence databases and functionally classified. Data were specifically searched for sequences related to carbohydrate metabolism. Season wide evolution of functional classes was evaluated by comparing libraries at the level of functional categories and unigenes distribution.</p> <p>Conclusion</p> <p>This chicory EST dataset provides a season wide outlook of the genes expressed in the root and to a minor extent in leaves and nodules. The dataset contains more than 200 sequences related to carbohydrate metabolism and 3,500 new ESTs when compared to other recently released chicory EST datasets, probably because of the season wide coverage of the root samples. We believe that these sequences will contribute to accelerate research and breeding of the industrial chicory as well as of closely related species.</p

A phase II multicentre, open-label, proof-of-concept study of tasquinimod in hepatocellular, ovarian, renal cell, and gastric cancers

Background: Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. Patients and Methods: This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. Results: Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). Conclusions: This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. Trial registration: NCT01743469

Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks

<p>Abstract</p> <p>Background</p> <p>The identification of genomic signatures of colorectal cancer for risk stratification requires the study of large series of cancer patients with an extensive clinical follow-up. Multicentric clinical studies represent an ideal source of well documented archived material for this type of analyses.</p> <p>Methods</p> <p>To verify if this material is technically suitable to perform matrix-CGH, we performed a pilot study using macrodissected 29 formalin-fixed, paraffin-embedded tissue samples collected within the framework of the EORTC-GI/PETACC-2 trial for colorectal cancer. The scientific aim was to identify prognostic genomic signatures differentiating locally restricted (UICC stages II-III) from systemically advanced (UICC stage IV) colorectal tumours.</p> <p>Results</p> <p>The majority of archived tissue samples collected in the different centers was suitable to perform matrix-CGH. 5/7 advanced tumours displayed 13q-gain and 18q-loss. In locally restricted tumours, only 6/12 tumours showed a gain on 13q and 7/12 tumours showed a loss on 18q. Interphase-FISH and high-resolution array-mapping of the gain on 13q confirmed the validity of the array-data and narrowed the chromosomal interval containing potential oncogenes.</p> <p>Conclusion</p> <p>Archival, paraffin-embedded tissue samples collected in multicentric clinical trials are suitable for matrix-CGH analyses and allow the identification of prognostic signatures and aberrations harbouring potential new oncogenes.</p

A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

International audienceBackground: Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity.Methods: We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced.Results: Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients.Conclusion: This preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit

Combined detailed and quasi steady-state time simulations for large-disturbance analysis

This paper deals with the simulation of long-term responses of power systems to large disturbances in the presence of discrete events. After outlining the power system model under the quasi steady-state (QSS) approximation, a method combining detailed and QSS time simulations is presented, the former being used for accuracy and the latter for efficiency reasons. Detailed time simulation is used to analyze the short-term period following a large disturbance and identify the discrete controls triggered. Next, QSS simulation is used to simulate the same time interval with the discrete controls imposed as external events, before letting the system evolve as usual in the long-term. This simple method has been successfully tested on the Hydro-Quebec system. (C) 2006 Elsevier Ltd. All rights reserved

Eléments aléatoires à valeurs convexes compactes

Université : Université scientifique et médicale de Grenobl

Undervoltage load shedding scheme for the Hydro-Québec system

In recent years, Hydro-Québec has undertaken a major program to upgrade the reliability of its transmission system. Much effort has been focused on increasing the system's ability to withstand extreme contingencies, usually caused by multiple incidents or the successive tripping of transmission lines. This paper deals with the conception and the control logic of an undervoltage load shedding scheme aimed at protecting the Hydro-Québec system against long-term voltage instability. Various results showing the impact of the operation of these automatisms on the system stability are provided in this paper