Menée en France sur 233 patientes atteintes d'un cancer du sein traité entre 2004 et 2008, cette étude prospective multicentrique non randomisée compare la faisabilité et la reproductibilité de trois systèmes de radiothérapie conformationnelle avec asservissement respiratoire

Contribution of Respiratory Gating Techniques for Optimization of Breast Cancer Radiotherapy

Giraud, Philippe ; Djadi-Prat, Juliette ; Morelle, Magalie ; Pourel, Nicolas ; Durdux, Catherine ; Carrie, Christian ; Daveau, Caroline ; Carrère, Marie-Odile ; , the STIC study centers

A comparative, nonrandomized, multicenter, and prospective analysis were performed between April 2004 and June 2008 in 20 French centers in order to compare clinical aspects of respiratory-gated conformal radiotherapy (RGRT) during breast cancer irradiation versus conventional conformal radiotherapy. The final results based on 233 evaluable patients at 48 months confirm the feasibility and good reproducibility of the RGRT systems. The main results demonstrated a marked reduction of dosimetric [...]

A partir de données d'un registre médical portant sur 356 patients atteints d'un cancer localisé de la prostate de stade T1-T2 et ayant subi une résection complète par ultrasons focalisés de haute intensité entre 1994 et 2009 (durée médiane de suivi : 2,8 ans), cette étude multicentrique évalue le risque de récidive biochimique et le taux de survie sans progression de la maladie à 5 et 7 ans

Complete high-intensity focused ultrasound in prostate cancer: outcome from the @-Registry

Blana, A. ; Robertson, C. N. ; Brown, S. C. W. ; Chaussy, C. ; Crouzet, S. ; Gelet, A. ; Conti, G. N. ; Ganzer, R. ; Pasticier, G. ; Thuroff, S. ; Ward, J. F.

Background : To analyze data on patients with localized prostate cancer who were treated with complete high-intensity focused ultrasound (HIFU) prospectively captured within a voluntary HIFU user database (@-Registry). Methods : The @-Registry includes data from consecutive patients treated with Ablatherm (EDAP-TMS) HIFU at nine European Centres during the period 1994 and 2009. For this analysis, the data repository was reviewed for information on patients with localized prostate cancer (T1–T2) [...]

Mené sur 100 patientes atteintes d'un cancer du sein de stade 0-IIA, cet essai prospectif définit la position individuelle optimale permettant de traiter par rayonnements ionisants des tumeurs mammaires sans endommager le système cardiovasculaire et les poumons

Prospective Assessment of Optimal Individual Position (Prone Versus Supine) for Breast Radiotherapy: Volumetric and Dosimetric Correlations in 100 Patients

Lymberis, Stella C. ; deWyngaert, John Keith ; Parhar, Preeti ; Chhabra, Arpit M. ; Fenton-Kerimian, Maria ; Chang, Jengwha ; Hochman, Tsivia ; Guth, Amber ; Roses, Daniel ; Goldberg, Judith D. ; Formenti, Silvia C.

Damage to heart and lung from breast radiotherapy is associated with increased cardiovascular mortality and lung cancer development. We conducted a prospective study to evaluate which position is best to spare lung and heart from radiotherapy exposure. One hundred consecutive Stage 0–IIA breast cancer patients consented to participate in a research trial that required two computed tomography simulation scans for planning both supine and prone positions. The optimal position was defined as that [...]

Mené sur 100 patientes ménopausées atteintes d'un cancer du sein de stade 1 et ayant reçu un traitement chirurgical conservateur (âge : 53 à 88 ans ; durée médiane de suivi : 64 mois), cet essai prospectif évalue sur 5 ans l'efficacité et la toxicité d'une irradiation partielle accélérée du sein par radiothérapie conformationnelle externe à trois dimensions

Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Five-year Results of 100 Patients

Formenti, Silvia C. ; Hsu, Howard ; Fenton-Kerimian, Maria ; Roses, Daniel ; Guth, Amber ; Jozsef, Gabor ; Goldberg, Judith D. ; DeWyngaert, J. Keith

To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position. Postmenopausal patients with Stage I breast cancer with nonpalpable tumors <2 cm, negative margins and negative nodes, positive hormone receptors, and no extensive intraductal component were eligible. The trial was offered only after eligible patients had refused to undergo standard whole-breast [...]

Menée in vivo et à l'aide d'un modèle mathématique, cette étude évalue la dimension optimale des nanoparticules destinées à pénétrer à l'intérieur des tumeurs

Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner

Chauhan, Vikash P. ; Stylianopoulos, Triantafyllos ; Martin, John D. ; Popovic, Zoran ; Chen, Ou ; Kamoun, Walid S. ; Bawendi, Moungi G. ; Fukumura, Dai ; Jain, Rakesh K.

The blood vessels of cancerous tumours are leaky and poorly organized. This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery. Anti-angiogenic therapies—which ‘normalize’ the abnormal blood vessels in tumours by making them less leaky—have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular weights, but it remains unclear whether normalizing tumour vessels can improve the delivery of [...]

Menée in vitro et in vivo, cette étude suggère que l'inhibition d'une enzyme surexprimée dans les cellules cancéreuses, l'anhydrase carbonique de type IX, augmente l'efficacité du bevacizumab

Carbonic anhydrase IX promotes tumour growth and necrosis in vivo and inhibition enhances anti-VEGF therapy

McIntyre, Alan ; Patiar, Shalini ; Wigfield, Simon ; Li, Ji-Liang ; Ledaki, Ioanna ; Turley, Helen ; Leek, Russell ; Snell, Cameron ; Gatter, Kevin C. ; Sly, William S. ; Vaughan-Jones, Richard D. ; Swietach, Pawel ; Harris, Adrian L.

Purpose:Bevacizumab, an anti-VEGFA antibody, inhibits the developing vasculature of tumours, but resistance is common. Antiangiogenic therapy induces hypoxia and we observed increased expression of hypoxia-regulated genes, including carbonic anhydrase IX (CAIX), in response to Bevacizumab treatment in xenografts. CAIX expression correlates with poor prognosis in most tumour types and with worse outcome in Bevacizumab-treated metastatic colorectal cancer patients, malignant astrocytoma and [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'intérêt d'un traitement combinant un composé appelé PF-03084014, un inhibiteur de gamma secrétase, et des glucorticoïdes chez des patients atteints d'un lymphome ou d'une leucémie lymphoblastique aiguë à cellules T

Preclinical analysis of the gamma-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia

Samon, Jeremy B. ; Castillo-Martin, Mireia ; Hadler, Michael ; Ambesi-Impiombato, Alberto ; Paietta, Elisabeth ; Racevskis, Janis ; Wiernik, Peter H. ; Rowe, Jacob M. ; Jakubczak, John L. ; Randolph, Sophia ; Cordon-Cardo, Carlos ; Ferrando, Adolfo A.

T-cell acute lymphoblastic leukemias and lymphomas (T-ALL) are aggressive hematologic cancers frequently associated with activating mutations in NOTCH1. Early studies identified NOTCH1 as an attractive therapeutic target for the treatment of T-ALL through the use of γ-secretase inhibitors (GSIs). Here, we characterized the interaction between PF-03084014, a clinically-relevant GSI, and dexamethasone in preclinical models of glucocorticoid-resistant T-ALL. Combination treatment of the GSI [...]

Mené sur 15 patients atteints d'une leucémie lymphocytaire chronique, cet essai de phase I évalue une immunothérapie à base d'un adénovirus codant pour la protéine chimérique CD154

Gene immunotherapy of chronic lymphocytic leukemia: a Phase I study of intranodally injected adenovirus expressing a chimeric CD154 molecule

Castro, Januario E ; Melo-Cardenas, Johanna ; Urquiza, Mauricio ; Barajas-Gamboa, Juan S ; Pakbaz, Ramin S ; Kipps, Thomas J.

New therapies for chronic lymphocytic leukemia (CLL) are needed, particularly those that can eradicate residual disease and elicit anti-CLL immune responses. CD40 ligation on CLL cells, which can be achieved using adenovirus encoding chimeric CD154 (Ad-ISF35), enhances their ability to function as antigen presenting cells and increases their sensitivity to clearance by immune-effector mechanisms. In this study, we report the results of a first-in-man Phase I trial of intranodal direct injection [...]

Menée sur des lignées cellulaires de cancer ovarien, cette étude évalue l'intérêt de développer des inhibiteurs de mTOR à large spectre ou des inhibiteurs d'un seul complexe, mTORC1 ou mTORC2

Predominance of mTORC1 over mTORC2 in the regulation of proliferation of ovarian cancer cells: therapeutic implications

Montero, Juan Carlos ; Chen, Xi ; Ocana, Alberto ; Pandiella, Atanasio

mTOR is a serine/threonine kinase which acts by binding different sets of proteins forming two complexes, termed mTORC1 and mTORC2. mTOR is deregulated in a substantial proportion of ovarian tumours. Despite the use of drugs directed to mTOR in ongoing clinical trials, the functional relevance of the individual mTORC branches in ovarian cancer is not known. Here we show that mTORC1 and mTORC2 were constitutively active in ovarian cancer cell lines. Knockdown of Raptor or Rictor, proteins [...]

Mené sur 39 patients atteints d'un cancer du poumon à petites cellules, cet essai de phase II évalue la toxicité et l'efficacité du nativoclax, un inhibiteur de Bcl-2 et Bcl-xL

Phase 2 Study of Single Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer

Rudin, Charles M. ; Hann, Christine L ; Garon, Edward B ; Ribeiro de Oliveira, Moacyr ; Bonomi, Philip D ; Camidge, D. Ross ; Chu, Quincy ; Giaccone, Giuseppe ; Khaira, Divis ; Ramalingam, Suresh S ; Ranson, Malcolm R ; Dive, Caroline ; McKeegan, Evelyn M ; Chyla, Brenda J ; Dowell, Barry L ; Chakravartty, Arunava ; Nolan, Cathy E ; Rudersdorf, Niki ; Busman, Todd A ; Mabry, Mack H ; Krivoshik, Andrew P ; Humerickhouse, Rod A ; Shapiro, Geoffrey I. ; Gandhi, Leena

Purpose: Bcl-2 is a critical regulator of apoptosis that is overexpressed in the majority of small cell lung cancers (SCLC). Nativoclax (ABT-263) is a potent and selective inhibitor of Bcl-2 and Bcl-xL. The primary objectives of this Phase 2a study included safety at the recommended Phase 2 dose and preliminary, exploratory efficacy assessment in patients with recurrent and progressive SCLC after at least one prior therapy. Experimental Design: 39 patients received navitoclax 325mg daily, [...]

Menée sur des lignées cellulaires de cancer de la prostate, cette étude identifie un nouvel antagoniste du récepteur aux androgènes, MEL-3, et caractérise son activité

Identification and characterization of MEL-3, a novel androgen receptor antagonist that suppresses prostate cancer cell growth

Helsen, Christine ; Marchand, Arnaud ; Chaltin, Patrick ; Munck, Sebastian ; Voet, Arnout ; Verstuyf, Annemieke ; Claessens, Frank

Anti-androgens are an important component of prostate cancer therapy as the androgen receptor (AR) is the key regulator of prostate cancer growth and survival. Current AR-antagonists, such as Bicalutamide (Bic) and Hydroxyflutamide (HOFl), have a low affinity for the AR and as a result block AR-signaling insufficiently. Moreover, many patients develop a resistance for Bic or HOFl during therapy or show a clinical improvement after withdrawal of the anti-androgen. New and more effective [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'une petite molécule inhibitrice de la voie de signalisation du facteur induit par l'hypoxie HIF-1

The HIF-pathway inhibitor NSC-134754 induces metabolic changes and anti-tumour activity while maintaining vascular function

Baker, L. C. J. ; Boult, J. K. R. ; Walker-Samuel, S. ; Chung, Y. L. ; Jamin, Y. ; Ashcroft, M. A. ; Robinson, S. P.

Background: Hypoxia-inducible factor-1 (HIF-1) mediates the transcriptional response to hypoxic stress, promoting tumour progression and survival. This study investigated the acute effects of the small-molecule HIF-pathway inhibitor NSC-134754. Methods: Human PC-3LN5 prostate cancer cells were treated with NSC-134754 for 24 h in hypoxia. Orthotopic prostate tumour-bearing mice were treated with a single dose of NSC-134754 for 6, 24 or 48 h. Treatment response was measured using magnetic [...]

Menée in vitro, cette étude évalue les effets d'une petite molécule, une dibenzophénanthridine inhibitrice d'une enzyme du métabolisme, la glutaminase C, sur la prolifération de cellules de cancer du sein

Dibenzophenanthridines as inhibitors of phosphate-activated glutaminase C and cancer cell proliferation

Katt, William P. ; Ramachandran, Sekar ; Erickson, Jon W. ; Cerione, Richard A.

One of the hallmarks of cancer cells is their adaptation to rely upon an altered metabolic scheme that includes changes in the glycolytic pathway, known as the Warburg effect, and elevated glutamine metabolism. As a consequence of these metabolic changes, cancer cells are often described as being addicted to glutamine. Glutaminase, a mitochondrial enzyme, plays a key role in the metabolism of glutamine in cancer cells, and thus its inhibition could significantly impact malignant transformation. [...]

Cet article passe en revue les perspectives offertes par le développement de thérapies ciblées pour surmonter la résistance à une hormonothérapie chez des patientes atteintes d'un cancer du sein métastatique

Targeted agents to reverse resistance to endocrine therapy in metastatic breast cancer: Where are we now and where are we going?

Fedele, Palma ; Calvani, Nicola ; Marino, Antonella ; Orlando, Laura ; Schiavone, Paola ; Quaranta, Annamaria ; Cinieri, Saverio

Endocrine therapy is the most important systemic therapy for hormone receptor positive breast cancer; however, some patients with ER+ breast cancer show intrinsic resistance to endocrine therapy, whereas others develop acquired resistance. Preclinical models have shown that endocrine resistance is associated with enhanced expression of membrane growth factor pathways or activation of various intracellular pathways involved in signal transduction and cell survival. Despite encouraging [...]

Menée sur des lignées cellulaires de cancer du sein triplement négatif et à l'aide d'un modèle murin, cette étude met en évidence des mécanismes associés à la résistance à un traitement par inhibiteur de MEK

Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer

Duncan, James S ; Whittle, Martin C ; Nakamura, Kazuhiro ; Abell, Amy N ; Midland, Alicia A ; Zawistowski, Jon S ; Johnson, Nancy L ; Granger, Deborah A ; Jordan, Nicole Vincent ; Darr, David B ; Usary, Jerry ; Kuan, Pei-Fen ; Smalley, David M ; Major, Ben ; He, Xiaping ; Hoadley, Katherine A ; Zhou, Bing ; Sharpless, Norman E ; Perou, Charles M ; Kim, William Y ; Gomez, Shawn M ; Chen, Xin ; Jin, Jian ; Frye, Stephen V ; Earp, H.  Shelton ; Graves, Lee M ; Johnson, Gary L

Kinase inhibitors have limited success in cancer treatment because tumors circumvent their action. Using a quantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple-negative breast cancer (TNBC) cells and genetically engineered mice (GEMMs). MEK inhibition caused acute ERK activity loss, resulting in rapid c-Myc degradation that induced expression and activation of several receptor tyrosine kinases (RTKs). RNAi knockdown of ERK or c-Myc mimicked RTK [...]

Menée sur 321 patients atteints d'un myélome multiple et inclus dans un essai de phase III, cette étude compare l'efficacité de deux traitements de consolidation après une greffe autologue de cellules souches hématopoïétiques

Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma

Cavo, Michele ; Pantani, Lucia ; Petrucci, Maria Teresa ; Patriarca, Francesca ; Zamagni, Elena ; Donnarumma, Daniela ; Crippa, Claudia ; Boccadoro, Mario ; Perrone, Giulia ; Falcone, Antonietta ; Nozzoli, Chiara ; Zambello, Renato ; Masini, Luciano ; Furlan, Anna ; Brioli, Annamaria ; Derudas, Daniele ; Ballanti, Stelvio ; Dessanti, Maria Laura ; De Stefano, Valerio ; Carella, Angelo Michele ; Marcatti, Magda ; Nozza, Andrea ; Ferrara, Felicetto ; Callea, Vincenzo ; Califano, Catello ; Pezzi, Annalisa ; Baraldi, Anna ; Grasso, Mariella ; Musto, Pellegrino ; Palumbo, Antonio

ABSTRACT In a randomized, phase 3 study, superior complete/near complete response (CR/nCR) rates and extended progression-free survival (PFS) were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autotransplantation (ASCT) for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n=236; TD, n=238). This per-protocol analysis (VTD, n=160; TD, n=161) was aimed to [...]

Menée sur 72 patients atteints d'un cancer colorectal métastatique sans mutation du gène KRAS et traités par irinotecan et cetuximab, cette étude montre que l'expression des kinases AKT et MAPK phosphorylées dans les métastases est associée à la résistance aux anticorps ciblant EGFR

Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab

Scartozzi, Mario ; Giampieri, Riccardo ; Maccaroni, Elena ; Mandolesi, Alessandra ; Biagetti, Simona ; Alfonsi, Simona ; Giustini, Lucio ; Loretelli, Cristian ; Faloppi, Luca ; Bittoni, Alessandro ; Bianconi, Maristella ; Del Prete, Michela ; Bearzi, Italo ; Cascinu, Stefano

BACKGROUND:Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation of the K- RAS gene. The EGFR pathway activation via the Ras-Raf-MAP-kinase and the protein-serine/threonine kinase AKT could determine resistance to anti-EGFR treatment.METHODS:We tested the interaction between phosphorylated AKT and MAPK expression in colorectal tumours and [...]

Cet article passe en revue les travaux récents sur les traitements d'un carcinome métastatique à cellules rénales

Treatment selection in metastatic renal cell carcinoma: expert consensus

Escudier, Bernard ; Szczylik, Cezary ; Porta, Camillo ; Gore, Martin

In metastatic renal cell carcinoma (mRCC), many factors influence clinical decisions, including histology, tumour burden, prognostic factors, comorbidities, and the ability of the patient to tolerate treatment. Progression-free survival (PFS) durations reported from randomized trials of targeted therapies vary considerably, in part because of differences in patient characteristics. For first-line therapy, an estimate of PFS with sunitinib, bevacizumab plus interferon, or sorafenib in a [...]

Cet article passe en revue les travaux récents sur le traitement des tumeurs primitives du cerveau chez l'adulte

Primary brain tumours in adults

Ricard, Damien ; Idbaih, Ahmed ; Ducray, François ; Lahutte, Marion ; Hoang-Xuan, Khê ; Delattre, Jean-Yves

Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas?the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the [...]

A partir de données cliniques provenant de 12 centres américains de greffes d'organes et portant sur 287 patients atteints d'un cholangiocarcinome périhilaire non résécable, cette étude évalue, du point de vue de la survie sans récidive à 5 ans et en fonction des caractéristiques tumorales, l'efficacité d'une chimioradiothérapie néoadjuvante avant une greffe de foie

Efficacy of Neoadjuvant Chemoradiation, followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers

Murad, Sarwa Darwish ; Kim, W. Ray ; Harnois, Denise M. ; Douglas, David D. ; Burton, James ; Kulik, Laura M. ; Botha, Jean F. ; Mezrich, Joshua D. ; Chapman, William C. ; Schwartz, Jason J. ; Hong, Johnny C. ; Emond, Jean C. ; Jeon, Hoonbae ; Rosen, Charles B. ; Gores, Gregory J. ; Heimbach, Julie K.

Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing (UNOS) to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception. We collected and analyzed data from 12 large-volume transplant centers in the US. These [...]

Mené sur 392 patients atteints d'un cancer rectal localement avancé (âge : 18 ans ou plus ; durée médiane de suivi : 52 mois), cet essai multicentrique de phase 3 compare, du point de vue de la survie globale à 5 ans et des événements indésirables, l'efficacité et la toxicité de deux chimioradiothérapies, l'une par capécitabine et l'autre par fluorouracile

Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial

Hofheinz, Ralf-Dieter ; Wenz, Frederik ; Post, Stefan ; Matzdorff, Axel ; Laechelt, Stephan ; Hartmann, Jörg T. ; Müller, Lothar ; Link, Hartmut ; Moehler, Markus ; Kettner, Erika ; Fritz, Elisabeth ; Hieber, Udo ; Lindemann, Hans Walter ; Grunewald, Martina ; Kremers, Stephan ; Constantin, Christian ; Hipp, Matthias ; Hartung, Gernot ; Gencer, Deniz ; Kienle, Peter ; Burkholder, Iris ; Hochhaus, Andreas

Fluorouracil-based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine. This randomised, open-label, multicentre, non-inferiority, phase 3 trial began in March, 2002, as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy, in patients aged 18 years or older with pathological stage II?III [...]

A partir des données de deux essais de phase III évaluant un traitement néoadjuvant et incluant 1 767 patients atteints d'un cancer rectal de stade T3-4 (durée médiane de suivi : 5,6 ans), cette étude évalue, du point de vue de la survie globale, du contrôle de la maladie et de la réponse au traitement, l'intérêt d'une chimioradiothérapie pré-opératoire à base de 5-fluorouracile / leucovorine

What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: Surrogacy in question?

Bonnetain, F. ; Bosset, J. F. ; Gerard, J. P. ; Calais, G. ; Conroy, T. ; Mineur, L. ; Bouché, O. ; Maingon, P. ; Chapet, O. ; Radosevic-Jelic, L. ; Methy, N. ; Collette, L.

Background : Two phase III trials of neoadjuvant treatment in T3-4 rectal cancer established that adding chemotherapy (CRT) to radiotherapy (RT) improves pathological complete response (pCR) and local control (LC). We combined trials to assess the clinical benefit of CRT on overall (OS) and progression free survival (PFS) and to explore the surrogacy of pCR and LC. Patients and methods : Individual patient data from European Organisation for Research and Treatment of Cancer (EORTC) 22921 (1011 [...]

Cet article présente les résumés d'un symposium organisé par une société savante américaine sur l'implication des chercheurs fondamentaux dans les activités de recherche translationnelle

Engaging basic scientists in translational research: identifying opportunities, overcoming obstacles

Hobin, Jennifer ; Deschamps, Anne ; Bockman, Richard ; Cohen, Stanley ; Dechow, Paul ; Eng, Charis ; Galey, William ; Morris, Marianna ; Prabhakar, Sharma ; Raj, Usha ; Rubenstein, Peter ; Smith, John ; Stover, Patrick ; Sung, Nancy ; Talman, William ; Galbraith, Richard

This report is based on the Federation of American Societies for Experimental Biology's symposium, "Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles," held in Chevy Chase, MD, March 24-25, 2011. Meeting participants examined the benefits of engaging basic scientists in translational research, the challenges to their participation in translational research, and the roles that research institutions, funding organizations, professional societies, [...]

Signé par des responsables d'autorités réglementaires européennes, cet article analyse les enjeux du libre accès aux données d'essais cliniques

Open Clinical Trial Data for All? A View from Regulators

Eichler, Hans-Georg ; Abadie, Eric ; Breckenridge, Alasdair ; Leufkens, Hubert ; Rasi, Guido

Hans-Georg Eichler from the European Medicines Agency and colleagues provide a view from regulators on access to clinical trial data.

Cet article passe en revue les perspectives thérapeutiques offertes par le ciblage de protéines impliquées dans la régulation épigénétique de l'expression des gènes

Epigenetic protein families: a new frontier for drug discovery

Arrowsmith, Cheryl H. ; Bountra, Chas ; Fish, Paul V. ; Lee, Kevin ; Schapira, Matthieu

Epigenetic regulation of gene expression is a dynamic and reversible process that establishes normal cellular phenotypes but also contributes to human diseases. At the molecular level, epigenetic regulation involves hierarchical covalent modification of DNA and the proteins that package DNA, such as histones. Here, we review the key protein families that mediate epigenetic signalling through the acetylation and methylation of histones, including histone deacetylases, protein methyltransferases, [...]