1,745,173 research outputs found
Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naïve patients.
No full textEcteinascidin 743 (ET-743; Yondelis, Trabectedin) is a marine anticancer agent that induces long-lasting objective remissions and tumor control in a subset of patients with pretreated/resistant soft-tissue sarcoma. Drug-induced tumor control is achievable in 22% of such patients, but there is no clear indication of the molecular features correlated with clinical sensitivity/resistance to ET-743. Nine low-passage, soft-tissue sarcoma cell lines, explanted from chemo-naive patients with different patterns of sensitivity, have been profiled with a cDNA microarray containing 6,700 cancer-related genes. The molecular signature of these cell lines was analyzed at baseline and at four different times after ET-743 exposure. The association of levels of TP53 mutation and TP73 expression with ET-743 sensitivity and cell cycle kinetics after treatment was also analyzed. Gene expression profile analysis revealed up-regulation of 86 genes and down-regulation of 244 genes in response to ET-743. The ET-743 gene expression signature identified a group of genes related with cell cycle control, stress, and DNA-damage response (JUNB, ATF3, CS-1, SAT, GADD45B, and ID2) that were up-regulated in all the cell lines studied. The transcriptional signature 72 hours after ET-743 administration, associated with ET-743 sensitivity, showed a more efficient induction of genes involved in DNA-damage response and apoptosis, such as RAD17, BRCA1, PAR4, CDKN1A, and P53DINP1, in the sensitive cell line group. The transcriptional signature described here may lead to the identification of ET-743 downstream mediators and transcription regulators and the proposal of strategies by which ET-743-sensitive tumors may be identified.1,83 M
Resolución UNRN N° 743/2009. Convoca expositores en la Jornada sobre "Responsabilidad del Estado"
No full textFil: Universidad Nacional de Río Negro (U). Universidad Nacional de Río Negro. Río Negro, ArgentinaResolución UNRN N° 743/2009. Convoca expositores en la Jornada sobre "Responsabilidad del Estado"fals
Synthetic studies of ecteinascidin 743 and fennebricin B
Full text link2017 Fall.Includes bibliographical references.Ecteinascidin 743 (Et-743, trabectidin or Yondelis®) possesses an impressive antitumor activity that it was approved for treatments of several cancer types worldwide. Since this natural product only presents as a trace amount in the nature, the main supply of this drug for research and commercial use is from laboratory synthesis. Many syntheses of Et-743 have been reported including three total syntheses, two formal syntheses and two semisyntheses. The biological activities of fennebricin B were unknown due to the scarcity of this natural product. However, fennebricin B share a common pentacyclic core with Et-743, thus may also possess interesting biological activities. Our group completed our formal synthesis of the natural product in 2008, featuring the Pictet-Spengler reaction to construct the pentacyclic core of Et-743. Our work, however, also produced both desired and undesired pentacycle without selectivity. We herein described an improved formal synthesis of Et-743 employing bromine auxiliary to generate the pentacylic core of Et-743 with the desired regioisomer as the only product. This approach was also utilized in the synthetic studies toward the total synthesis of fennebricin B
Specialty farming in Idaho: Is it for me?
No full textBulletin no. 743 Moscow, Idaho :University of Idaho, College of Agriculture, Cooperative Extension System, 1992-01-01. Author(s): Barney, D.L.; Finnerty, T.L. ; Laughlin, K.M
Investigation into the hepatotoxicity of the novel anti-cancer drug ecteinascidin-743 (ET-743).
No full textEcteinascidin-743 (ET-743) is a novel marine-derived anti-cancer drug with demonstrated anti-tumour activity in clinical trials against sarcoma, breast and ovarian carcinoma. Reversible transaminitis and subclinical cholangitis have frequently been described in patients who receive ET-743. To facilitate understanding of this adverse effect and help design suitable therapeutic rescue strategies, the hepatic effects of ET-743, administered as a single i.v. dose of 40 ?.g/kg, were characterised in female Wistar rats by histopathology, electron microscopy, hepatic and plasma biochemistry and DNA microarray analysis. Plasma levels of bilirubin were elevated up to 7-fold over those in untreated rats and activities of alkaline phosphatase and aspartate aminotransferase in plasma were slightly elevated. Livers displayed degeneration and necrosis of bile duct epithelia associated with mild inflammation followed by fibrosis. DNA microarray analysis of livers from ET-743-treated rats showed a significant increase in the expression of ATP binding cassette transport genes abcbla and abcblb and cell cycle genes cdc2a and ccndl. The cell cycle gene expression changes mirrored ET-743- induced increases in liver weight and Ki-67 labelling of liver nuclei. The results suggest that the toxicity exerted by ET-743 in the rat liver is a consequence of biliary damage and is accompanied by a wave of mitogenic activity. Pre-treatment with dexamethasone (10 mg/kg p.o.) 24 hours prior to ET-743 abrogated the biochemical and histopathological manifestations of ET-743-induced liver changes without interfering with the anti-tumour activity. Dexamethasone pre-treatment decreased hepatic levels of ET-743 dramatically compared to those obtained after administration of ET-743 alone. Pre-treatment with dexamethasone effectively protected against ET-743-mediated hepatic damage by decreasing hepatic exposure to ET-743, probably linked to induction of certain cytochrome P450 enzymes. Pre-treatment with cytochrome P450 inducers ?-naphthoflavone, phenobarbitone or indole-3-carbinol also reduced ET-743-mediated hepatotoxicity. In conclusion, the results strongly advocate the clinical evaluation of pretreatment with dexamethasone in patients who receive ET-743 to ameliorate its unwanted effects in the liver
Synthetic Studies toward Ecteinascidin 743
No full textAn efficient synthesis of a fully functionalized tetracyclic fragment (A-B-C-H) I of ecteinascidin 743, contg. a 1,4-bridged 10-membered lactone, is reported. The synthesis is highly convergent and has been carried out on a multigram scale featuring the following key steps: union of two fragments II and III via an oxazolidine intermediate; and acid-promoted macrocyclization via formation of a carbon-sulfur bond with concomitant formation of the 10-membered ring. Although compd. I was responsive to the intramol. Pictet-Spengler reaction, a destructive ring opening of the 1,4-bridged lactone also occurred, leading to the formation of pentacyclic compd. IV. In the course of this study, it was discovered that a combination of a mild Lewis acid and a mild Bronsted acid constituted excellent reagents for performing the Pictet-Spengler reaction of a highly acid-sensitive substrate. [on SciFinder (R)]LSPNCAN 143:6012531-6AlkaloidsInstitut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.Journalwritten in English.654644-01-6P Role: PRP (Properties), SPN (Synthetic preparation), PREP (Preparation) (crystal structure; synthetic studies toward ecteinascidin 743); 200132-54-3 Role: CAT (Catalyst use), USES (Uses) (synthetic studies toward ecteinascidin 743); 108-88-3 (Toluene); 920-66-1 Role: NUU (Other use, unclassified), USES (Uses) (synthetic studies toward ecteinascidin 743); 114899-77-3P (Ecteinascidin 743) Role: PNU (Preparation, unclassified), PREP (Preparation) (synthetic studies toward ecteinascidin 743); 106-95-6 (Allyl bromide); 488-17-5; 533-31-3 (1,3-Benzodioxol-5-ol); 924-44-7 (Ethyl glyoxylate); 2799-07-7; 3966-32-3; 26164-26-1; 81477-94-3; 95715-87-0; 96845-11-3 Role: RCT (Reactant), RACT (Reactant or reagent) (synthetic studies toward ecteinascidin 743); 111726-43-3P; 187040-02-4P; 187040-03-5P; 654643-96-6P; 654643-97-7P; 654643-98-8P; 654643-99-9P; 654644-00-5P; 654644-02-7P; 654644-03-8P; 654644-04-9P; 686776-20-5P; 686776-21-6P; 686776-22-7P; 686776-23-8P; 686776-24-9P; 686776-25-0P; 686776-28-3P; 686776-29-4P; 854021-71-9P; 854021-83-3P; 854021-99-1P; 854022-02-9P; 854022-04-1P; 854022-09-6P; 854022-14-3P; 854022-23-4P; 854022-25-6P; 854022-31-4P; 854022-33-6P; 854022-35-8P; 854022-39-2P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (synthetic studies toward ecteinascidin 743); 7447-41-8 (Lithium chloride) Role: RGT (Reagent), RACT (Reactant or reagent) (synthetic studies toward ecteinascidin 743); 654643-95-5P; 854021-95-7P; 854021-97-9P; 854022-01-8P; 854022-06-3P; 854022-12-1P; 854022-29-0P; 854022-37-0P Role: SPN (Synthetic preparation), PREP (Preparation) (synthetic studies toward ecteinascidin 743
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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SB 743 Implementation: Challenges and Opportunities
Full text linkCalifornia’s Senate Bill (SB) 743, enacted in 2013, marks a historic shift in how the traffic impacts of development projects are to be evaluated and mitigated statewide. To help achieve state climate policy and sustainability goals, SB 743 eliminates traffic delay as an environmental impact under the California Environmental Quality Act. State implementing guidelines for SB 743 instead require an assessment of vehicle miles traveled (VMT). The adoption of the guidelines sparked debate and raised far-reaching questions about development planning. Our research consisted of four parts. First, we considered how the state guidelines might be applied by analyzing travel patterns across and within California cities in relation to the guidelines. We also interviewed fortythree professional transportation consultants and regional and local planners to provide insights on SB 743 implementation. In addition, we carried out extensive case studies of San Francisco and Pasadena, where policies had already been adopted to align with SB 743. Finally, to help assess the technical challenges involved in SB 743 implementation, we tested two VMT estimation tools in common use and considered the practical challenges facing tool users. We find that SB 743 implementation is likely to present some transitional challenges for city planners, but the long-term prospects for improving transportation planning as a result of the law are promising
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