Menée sur 14 patients atteints d'un carcinome à cellules rénales de stade cT1 avec faible score de PADUA (durée médiane de suivi : 12 mois), cette étude évalue, du point de vue de la conservation des fonctions rénales et des complications, la toxicité et la faisabilité d'une néphrectomie partielle laparo-endoscopique avec accès unique et sans clampage

Clampless laparoendoscopic single-site partial nephrectomy for renal cancer with low PADUA score: technique and surgical outcomes

Springer, Christopher ; Veneziano, Domenico ; Wimpissinger, Florian ; Inferrera, Antonino ; Fornara, Paolo ; Greco, Francesco

What's known on the subject? and What does the study add? * Laparoendoscopic single-site (LESS) surgery has proved to be immediately applicable in the clinical field, being safe and feasible in the hands of experienced laparoscopic surgeons in well-selected patients. All extirpative and reconstructive urological procedures have been described in the literature, but LESS partial nephrectomy (PN) is one of the most complex procedures and few studies have been published on this subject. * The [...]

Menée sur une cohorte de 1 655 patients atteints d'un cancer de la prostate diagnostiqué en 1994 ou 1995 (âge au diagnostic : entre 55 et 74 ans), cette étude compare, du point de vue des fonctions urinaires, intestinales et sexuelles, les complications d'une radiothérapie et d'une prostatectomie radicale 2, 5 et 15 ans après le diagnostic

Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer

Resnick, Matthew J. ; Koyama, Tatsuki ; Fan, Kang-Hsien ; Albertsen, Peter C. ; Goodman, Michael ; Hamilton, Ann S. ; Hoffman, Richard M. ; Potosky, Arnold L. ; Stanford, Janet L. ; Stroup, Antoinette M. ; Van Horn, R. Lawrence ; Penson, David F.

Background : The purpose of this analysis was to compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy. Methods: The Prostate Cancer Outcomes Study (PCOS) enrolled 3533 men in whom prostate cancer had been diagnosed in 1994 or 1995. The current cohort comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). [...]

Mené sur 743 patients atteints d'un cancer de la prostate à haut risque de récidive, cette étude évalue, du point de vue de la qualité des marges de résection et de la récidive biochimique, l'efficacité d'une prostatectomie radicale rétropubienne par voie ouverte par rapport à une prostatectomie radicale laparoscopique assistée ou non par robot

Contemporaneous comparison of open vs minimally-invasive radical prostatectomy for high-risk prostate cancer

Pierorazio, Phillip M. ; Mullins, Jeffrey K. ; Eifler, John B. ; Voth, Kipp ; Hyams, Elias S. ; Han, Misop ; Pavlovich, Christian P. ; Bivalacqua, Trinity J. ; Partin, Alan W. ; Allaf, Mohamad E. ; Schaeffer, Edward M.

What's known on the subject? and What does the study add? The ideal treatment for men with high-risk prostate cancer is controversial, although most physicians agree that a multimodal approach, including radiation and hormone therapy with or without surgery, offers the best chance of cancer control. Minimally-invasive radical prostatectomy has emerged as a treatment option for clinically localized cancer; however, critics argue that the open approach may afford advantages of tactile feedback [...]

Menée sur 464 patients atteints d'un cancer de la prostate à risque élevé ou intermédiaire de récidive et traité entre 2006 et 2011 (durée médiane de suivi : 36 mois), cette étude coréenne compare, du point de vue du taux de détection de métastases ganglionnaires et du taux de survie sans récidive biochimique à 3 ans, l'efficacité d'une lymphadénectomie étendue et d'une lymphadénectomie standard lors d'une prostatectomie radicale assistée par robot

Extended vs standard lymph node dissection in robot-assisted radical prostatectomy for intermediate- or high-risk prostate cancer: a propensity-score-matching analysis

Kim, Kwang Hyun ; Lim, Sey Kiat ; Kim, Ha Yan ; Shin, Tae-Young ; Lee, Joo Yong ; Choi, Young Deuk ; Chung, Byung Ha ; Hong, Sung Joon ; Rha, Koon Ho

What's known on the subject? and What does the study add? * Although lymph node dissection (LND) is known as the most accurate method of nodal staging, the therapeutic role of LND remains undetermined. This is mainly because of the lack of randomized prospective studies and the fact that retrospective analyses often result in bias and misinterpretation. * To overcome the limitation of retrospective analysis, we matched preoperative variables using propensity scores and compared the outcomes [...]

Menée sur 538 patients atteints d'un cancer localisé de la prostate traité entre 1997 et 2009 (durée de suivi : 8,1 ans), cette étude rétrospective évalue, du point de vue de la survie et des effets indésirables, l'efficacité et la toxicité des ultrasons focalisés de haute intensité en premier traitement

Fourteen-year oncological and functional outcomes of high-intensity focused ultrasound in localized prostate cancer

Ganzer, Roman ; Fritsche, Hans-Martin ; Brandtner, Andreas ; Bründl, Johannes ; Koch, Daniel ; Wieland, Wolf F. ; Blana, Andreas

What's known on the subject? and What does the study add? * High-intensity focused ultrasound (HIFU) is an alternative treatment option for localized prostate cancer (PCa), which is applied for over 15 years. There are conflicting recommendations for HIFU among urological societies, which can be explained by the lack of prospective controlled studies, reports on preselected patient populations and limited follow-up providing little information on overall and cancer-specific survival. * We [...]

Menée pour la première fois sur des patients atteints de cancer avec métastases hépatiques, cette étude évalue la toxicité et l'activité antitumorale de petits ARNs interférents inclus dans des nanoparticules et ciblés sur VEGF et KSP

First-in-Man Trial of an RNA Interference Therapeutic Targeting VEGF and KSP in Cancer Patients with Liver Involvement

Tabernero, Josep ; Shapiro, Geoffrey I. ; LoRusso, Patricia M. ; Cervantes, Andres ; Schwartz, Gary K. ; Weiss, Glen J. ; Paz-Ares, Luis ; Cho, Daniel C. ; Infante, Jeffrey R. ; Alsina, Maria ; Gounder, Mrinal M. ; Falzone, Rick ; Harrop, Jamie ; Seila White, Amy C. ; Toudjarska, Iva ; Bumcrot, David ; Meyers, Rachel E. ; Hinkle, Gregory ; Svrzikapa, Nenad ; Hutabarat, Renta M. ; Clausen, Valerie A. ; Cehelsky, Jeff ; Nochur, Saraswathy V. ; Gamba-Vitalo, Christina ; Vaishnaw, Akshay K. ; Sah, Dinah W.Y. ; Gollob, Jared A. ; Burris, Howard A.

RNAi is a potent and specific mechanism for regulating gene expression. Harnessing RNAi to silence genes involved in disease holds promise for the development of a new class of therapeutics. Delivery is key to realizing the potential of RNAi, and lipid nanoparticles (LNPs) have proven effective in delivery of siRNAs to liver and tumors in animals. To examine the activity and safety of LNP-formulated siRNAs in man, we initiated a trial of ALN-VSP, an LNP formulation of siRNAs targeting VEGF and [...]

Menée sur des lignées cellulaires de mélanome, de cancers du poumon et du sein, cette étude évalue les perspectives offertes par le ciblage de composants du splicéosome pour le traitement des cancers

Targeting the deregulated spliceosome core machinery in cancer cells triggers mTOR blockade and autophagy

Quidville, Virginie ; Alsafadi, Samar ; Goubar, Aicha ; Commo, Frederic ; Scott, Veronique ; Durieu, Catherine ; Girault, Isabelle ; Baconnais, Sonia ; Lecam, Eric ; Lazar, Vladimir ; Delaloge, Suzette ; Saghatchian, Mahasti ; Pautier, Patricia ; Morice, Philippe ; Dessen, Philippe ; Vagner, Stephan ; Andre, Fabrice

The spliceosome is a large ribonucleoprotein complex that guides pre-mRNA splicing in eukaryotic cells. Here we determine whether the spliceosome could constitute an attractive therapeutic target in cancer. Analysis of gene expression arrays from lung, breast and ovarian cancers datasets revealed that several genes encoding components of the core spliceosome composed of a heteroheptameric Sm complex were overexpressed in malignant disease as compared to benign lesions, and could also define a [...]

Cet article passe en revue les travaux récents sur la toxicité des thérapies ciblées lorsqu'elles sont utilisées en combinaison pour le traitement des tumeurs solides

Safety and feasibility of targeted agent combinations in solid tumours

Park, Sook Ryun ; Davis, Myrtle ; Doroshow, James H. ; Kummar, Shivaani

The plethora of novel molecular-targeted agents (MTAs) has provided an opportunity to selectively target pathways involved in carcinogenesis and tumour progression. Combination strategies of MTAs are being used to inhibit multiple aberrant pathways in the hope of optimizing antitumour efficacy and to prevent development of resistance. While the selection of specific agents in a given combination has been based on biological considerations (including the role of the putative targets in cancer) [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'un nouveau composé appelé TAK-901, un inhibiteur de la kinase Aurora B

Biological Characterization of TAK-901, an Investigational, Novel, Multi-Targeted Aurora B Kinase Inhibitor

Farrell, Pamela ; Shi, Lihong ; Matuszkiewicz, Jennifer ; Balakrishna, Deepika ; Hoshino, Takashi ; Zhang, Lilly ; Elliott, Sarah ; Fabrey, Robyn ; Lee, Bumsup ; Halkowycz, Petro ; Sang, BiChing ; Ishino, Seigo ; Nomura, Toshiyuki ; Teratani, Mika ; Ohta, Yoshikazu ; Grimshaw, Charles ; Paraselli, Bheema ; Satou, Takashi ; de Jong, Ron

Protein kinases Aurora A, B, and C play essential roles during mitosis and cell division, are frequently elevated in cancer, and represent attractive targets for therapeutic intervention. TAK-901 is an investigational, multi-targeted Aurora B kinase inhibitor derived from a novel azacarboline kinase hinge-binder chemotype. TAK-901 exhibited time-dependent, tight-binding inhibition of Aurora B, but not Aurora A. Consistent with Aurora B inhibition, TAK-901 suppressed cellular histone H3 [...]

Menée sur des lignées cellulaires de mélanome présentant la mutation V600E du gène BRAF, cette étude met en évidence un mécanisme impliqué dans l'apparition d'une résistance au vemurafenib

Vemurafenib Potently Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in BRAFV600E Melanoma Cells

Beck, Daniela ; Niessner, Heike ; Smalley, Keiran S. M. ; Flaherty, Keith ; Paraiso, Kim H. T. ; Busch, Christian ; Sinnberg, Tobias ; Vasseur, Sophie ; Iovanna, Juan Lucio ; Driessen, Stefan ; Stork, Bjorn ; Wesselborg, Sebastian ; Schaller, Martin ; Biedermann, Tilo ; Bauer, Jurgen ; Lasithiotakis, Konstantinos ; Weide, Benjamin ; Eberle, Jurgen ; Schittek, Birgit ; Schadendorf, Dirk ; Garbe, Claus ; Kulms, Dagmar ; Meier, Friedegund

The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients with BRAFV600E-mutated melanoma, its effects are limited by the onset of drug resistance. We found that exposure of melanoma cell lines with the BRAFV600E mutation to vemurafenib [...]

Menée à l'aide de modèles murins, cette étude évalue l'activité antitumorale d'un traitement combinant le topotecan et une formulation liposomale de la doxorubicine pour le traitement d'un cancer de l'ovaire

Topotecan and Doxorubicin Combination to Treat Recurrent Ovarian Cancer: The Influence of Drug Exposure Time and Delivery Systems to Achieve Optimum Therapeutic Activity

Patankar, Nilesh A. ; Pritchard, Julia ; van Grinsven, Mariska ; Osooly, Maryam ; Bally, Marcel B.

Purpose: To provide proof-of-concept data to support use of Doxil–liposomal topotecan (Topophore C) combinations to treat ovarian cancer. Experimental Design: ES-2, OVCAR-3, and SKOV-3 ovarian cancer cell lines were treated with doxorubicin–topotecan combinations by exposing the cells to drugs from 1 to 72 hours. Pharmacokinetic analysis was conducted following administration of liposomal formulations of these drugs alone and in combination. Efficacy assessments were completed in ES-2 and [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme permettant de rendre compte de l'activité antitumorale de l'erlotinib en combinaison avec la gemcitabine dans l'adénocarcinome canalaire du pancréas

Erlotinib prolongs survival in pancreatic cancer by blocking gemcitabine-induced MAPK signals

Miyabayashi, Koji ; Ijichi, Hideaki ; Mohri, Dai ; Tada, Motohisa ; Yamamoto, Keisuke ; Asaoka, Yoshinari ; Ikenoue, Tsuneo ; Tateishi, Keisuke ; Nakai, Yousuke ; Isayama, Hiroyuki ; Morishita, Yasuyuki ; Omata, Masao ; Moses, Harold L. ; Koike, Kazuhiko

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the epidermal growth factor receptor (EGFR) inhibitor, erlotinib with gemcitabine has been the only molecular targeted drug tested so far which has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen remains unknown. Here we demonstrate that the combination is superior to gemcitabine alone [...]

Menée sur des lignées cellulaires de cancer du poumon non à petites cellules sans mutations du gène EGFR, cette étude met en évidence un mécanisme permettant de rendre compte de l'efficacité clinique de l'erlotinib, par comparaison avec le gefinitib qui n'est efficace qu'en présence de mutations activatrices du récepteur EGFR

Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib in EGFR Wild-type Non-small Cell Lung Carcinoma Cell Lines

Augustin, Angelique ; Lamerz, Jenz ; Meistermann, Helene ; Golling, Sabrina ; Scheiblich, Stefan ; Hermann, Johannes C ; Duchateau-Nguyen, Guillemette ; Tzouros, Manuel ; Avila, David W ; Langen, Hanno ; Essioux, Laurent ; Klughammer, Barbara

Although both erlotinib and gefitinib target the epidermal growth factor receptor (EGFR), erlotinib is effective in patients with EGFR wild-type or mutated tumors, whereas gefitinib is only beneficial for patients with activating mutations. To determine whether these differences in clinical outcomes can be attributed to their respective protein interaction profiles, a label-free, quantitative chemical proteomics study was performed. Using this method, 24 proteins were highlighted in the binding [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'un peptide hybride se liant au récepteur HER2 pour le traitement d'un cancer du sein HER2+

HER2-targeted hybrid peptide that blocks HER2 tyrosine kinase disintegrates cancer cell membrane and inhibits tumor growth in vivo

Kawamoto, Megumi ; Horibe, Tomohisa ; Kohno, Masayuki ; Kawakami, Koji

HER2 is a transmembrane oncoprotein encoded by the HER2/neu gene and is overexpressed in approximately 20-30% of breast cancers. We have recently designed a novel class of drug, the hybrid peptide, which is chemically synthesized and is composed of a target-binding peptide and a lytic peptide containing cationic-rich amino acid components that disintegrates the cell membrane leading to cancer cell death via membrane lysis. In this study, we designed a HER2-binding peptide linked to this novel [...]

Menée in vitro, cette étude évalue la faisabilité d'une méthode pour faire croître ex vivo des cellules NK activées à partir de cellules mononucléées du sang périphérique d'enfants atteints d'un neuroblastome à haut risque

Growth and Activation of Natural Killer Cells Ex Vivo from Children with Neuroblastoma for Adoptive Cell Therapy

Liu, Yin ; Wu, Hong-Wei ; Sheard, Michael A ; Sposto, Richard ; Somanchi, Srinivas S ; Cooper, Laurence JN ; Lee, Dean A ; Seeger, Robert C.

Purpose: Adoptive transfer of natural killer (NK) cells combined with tumor-specific monoclonal antibodies (mAbs) has therapeutic potential for malignancies. We determined if large numbers of activated NK (aNK) cells can be grown ex vivo from peripheral blood mononuclear cells (PBMC) of children with high-risk neuroblastoma using artificial antigen-presenting cells (aAPC). Experimental Design: Irradiated K562-derived Clone 9.mbIL21 aAPC were co-cultured with PBMC, and propagated NK cells were [...]

Mené sur 20 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai évalue la toxicité et les caractéristiques pharmacocinétiques d'un nouvel anticorps monoclonal appelé GC33

First-in-Man Phase I Study of GC33, A Novel Recombinant Humanized Antibody against Glypican-3, in Patients with Advanced Hepatocellular Carcinoma

Zhu, Andrew X. ; Gold, Philip J. ; El-khoueiry, Anthony ; Abrams, Thomas A. ; Morikawa, Hideo ; Ohishi, Nirihisa ; Ohtomo, Toshihiko ; Philip, Philip A.

Purpose:GC33 is a novel recombinant fully humanized monoclonal antibody that binds to human glypican-3 (GPC3). The anti-tumor activity of GC33 was demonstrated in preclinical models of hepatocellular carcinoma (HCC). This first-in-man clinical trial was conducted to evaluate the safety, pharmacokinetic (PK) characteristics, and preliminary efficacy of GC33 in patients with advanced HCC. Experimental Design:Patients with measurable, histologically proven, advanced HCC were enrolled to a [...]

Mené sur 492 patients atteints d'une leucémie lymphoblastique aiguë entre 1 et 18 ans, cet essai évalue la toxicité et l'efficacité d'un traitement combinant dexaméthasone et une nouvelle méthode de dosage de la L-asparaginase dérivé d'Escherichia coli

Postinduction Dexamethasone and Individualized Dosing of Escherichia Coli L-Asparaginase Each Improve Outcome of Children and Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia: Results From a Randomized Study—Dana-Farber Cancer Institute ALL Consortium Protocol 00-01

Vrooman, Lynda M. ; Stevenson, Kristen E. ; Supko, Jeffrey G. ; O'Brien, Jane ; Dahlberg, Suzanne E. ; Asselin, Barbara L. ; Athale, Uma H. ; Clavell, Luis A. ; Kelly, Kara M. ; Kutok, Jeffery L. ; Laverdière, Caroline ; Lipshultz, Steven E. ; Michon, Bruno ; Schorin, Marshall ; Relling, Mary V. ; Cohen, Harvey J. ; Neuberg, Donna S. ; Sallan, Stephen E. ; Silverman, Lewis B.

Purpose We assessed the toxicity and efficacy of dexamethasone and a novel dosing method of Escherichia coli L-asparaginase (EC-Asnase) in children and adolescents with newly diagnosed acute lymphoblastic leukemia (ALL). Patients and Methods Patients achieving complete remission (CR) on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 were eligible for random assignment to 1) dexamethasone or prednisone, administered as 5-day pulses, every 3 weeks, and 2) weekly EC-Asnase, [...]

Cet article passe en revue les travaux récents sur le traitement d'un lymphome diffus à grandes cellules B

Diffuse large B-cell lymphoma

Martelli, Maurizio ; Ferreri, Andrés J. M. ; Agostinelli, Claudio ; Di Rocco, Alice ; Pfreundschuh, Michael ; Pileri, Stefano A.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults accounting for 31% of all NHL in Western Countries. Following, morphological, biological and clinical studies have allowed the subdivision of DLBCLs into morphological variants, molecular and immunophenotypic subgroups and distinct disease entities. However, a large number of cases still remain biologically and clinically heterogeneous, for which there are no clear and accepted criteria for subclassification; [...]

Cet article passe en revue les travaux récents sur le choix du traitement initial et de la séquence des traitements ultérieurs pour les patients atteints d'un mélanome métastatique présentant la mutation V600E du gène BRAF

Which drug, and when, for patients with BRAF-mutant melanoma?

Jang, Sekwon ; Atkins, Michael B.

Patients with metastatic melanoma had few treatment options until 2011, when two drugs -ipilimumab and vemurafenib- were approved following advances in the understanding of melanoma biology and tumour immunology. Almost 50% of melanomas harbour mutations in BRAF, mainly at codon 600, which result in constitutive activation of the MAPK pathway. The selective inhibitors of mutant BRAF Val600, vemurafenib and dabrafenib, showed major tumour responses, resulting in improved progression-free and [...]

Mené sur 768 patients atteints d'un cancer colorectal métastatique, cet essai de phase III évalue, du point de vue de la survie sans progression, l'ajout de sunitinib à un protocole FOLFIRI

Fluorouracil, Leucovorin, and Irinotecan Plus Either Sunitinib or Placebo in Metastatic Colorectal Cancer: A Randomized, Phase III Trial

Carrato, Alfredo ; Swieboda-Sadlej, Anna ; Staszewska-Skurczynska, Marzanna ; Lim, Robert ; Roman, Laslo ; Shparyk, Yaroslav ; Bondarenko, Igor ; Jonker, Derek J. ; Sun, Yan ; De la Cruz, Jhony A. ; Williams, J. Andrew ; Korytowsky, Beata ; Christensen, James G. ; Lin, Xun ; Tursi, Jennifer M. ; Lechuga, Maria J. ; Van Cutsem, Eric

Purpose This double-blind, phase III study aimed to demonstrate that sunitinib plus FOLFIRI (fluorouracil, leucovorin, and irinotecan) was superior to placebo plus FOLFIRI in previously untreated metastatic colorectal cancer (mCRC). Patients and Methods Patients were randomly assigned to receive FOLFIRI and either sunitinib (37.5 mg per day) or placebo (4 weeks on treatment, followed by 2 weeks off [schedule 4/2]) until disease progression. The primary end point was progression-free survival [...]

Mené sur 7 576 patientes atteintes d'un cancer du sein de stade précoce après la ménopause (âge médian : 64,1 ans), cet essai de phase III compare, du point de vue de la survie sans événement à 5 ans, l'exémestane et l'anatrozole en traitement adjuvant

Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27—A Randomized Controlled Phase III Trial

Goss, Paul E. ; Ingle, James N. ; Pritchard, Kathleen I. ; Ellis, Matthew J. ; Sledge, George W. ; Budd, G. Thomas ; Rabaglio, Manuela ; Ansari, Rafat H. ; Johnson, David B. ; Tozer, Richard ; D'Souza, David P. ; Chalchal, Haji ; Spadafora, Silvana ; Stearns, Vered ; Perez, Edith A. ; Liedke, Pedro E.R. ; Lang, István ; Elliott, Catherine ; Gelmon, Karen A. ; Chapman, Judy-Anne W. ; Shepherd, Lois E.

Purpose In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non–cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. Patients and Methods We designed an open-label, randomized, phase III trial of [...]

Mené sur 41 patients atteints d'un glioblastome récidivant, cet essai de phase II évalue l'activité antitumorale du pazopanib en combinaison avec le lapatinib

A Phase I/II Trial of Pazopanib in Combination with Lapatinib in Adult Patients with Relapsed Malignant Glioma

Reardon, David A. ; Groves, Morris D. ; Wen, Patrick Y. ; Nabors, Louis B. ; Mikkelsen, Tom ; Rosenfeld, Steve ; Raizer, Jeffrey ; Barriuso, Jorge ; McLendon, Roger E. ; Suttle, A. Benjamin ; Ma, Bo ; Curtis, C. Martin ; Dar, Mohammed M. ; de Bono, Johann S.

Purpose: Increased mitogenic signaling and angiogenesis, frequently facilitated by somatic activation of EGFR (ErbB1) and/or loss of PTEN, and VEGF overexpression, respectively, drive malignant glioma growth. We hypothesized that recurrent glioblastoma patients would exhibit differential antitumor benefit based on tumor PTEN/EGFRvIII status when treated with the antiangiogenic agent pazopanib and the ErbB inhibitor lapatinib. Methods: A Phase II study evaluated the antitumor activity of [...]

Cet article passe en revue les études in vitro concernant les effets des inhibiteurs d'histones désacétylases, combinés à des rayonnements ionisants, sur les processus de signalisation associés à la réparation des dommages causés à l'ADN

Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair

Groselj, B. ; Sharma, N. L. ; Hamdy, F. C. ; Kerr, M. ; Kiltie, A. E.

Many cancers display increased expression of histone deacetylases (HDACs) and therefore transcriptionally inactive chromatin, resulting in the downregulation of genes including tumour suppressor and DNA repair genes. Histone deacetylase inhibitors (HDACi) are a heterogeneous group of epigenetic therapeutics, showing promising anticancer effects in both pre-clinical and clinical settings, in particular the effect of radiosensitisation when administered in combination with radiotherapy. [...]

Menée sur 44 patients atteints d'un carcinome de l'œsophage de stade II ou III, cette étude évalue, dans le cadre de la phase II d'un traitement trimodal, la dose maximale tolérée de capécitabine combinée de manière concomitante au docétaxel et à une radiothérapie thoracique

Trimodality Therapy for Stage II-III Carcinoma of the Esophagus: A Dose-Ranging Study of Concurrent Capecitabine, Docetaxel, and Thoracic Radiotherapy

Wood, Matthew D. ; Zaki, Bassem I. ; Gordon, Stuart R. ; Sutton, John E. Jr ; Lisovsky, Mikhail ; Gui, Jiang ; Bubis, Jeffrey A. ; Dragnev, Konstantin H. ; Rigas, James R.

Purpose: This dose-escalation study was performed to determine the recommended phase II dose of oral capecitabine to be delivered concurrently with thoracic radiation therapy and weekly docetaxel in patients with locally advanced esophageal carcinoma. Methods: Patients with operable stage II or III esophageal carcinoma were staged by endoscopic ultrasonography and computed tomography. Two cycles of docetaxel (80 mg/m2) and carboplatin (target area under the concentration-time curve: 6 mg/ml x [...]

Menée sur un modèle murin de sarcome, cette étude évalue l'efficacité d'un plasmide codant pour l'interleukine-12 et électro-transféré dans les cellules cancéreuses pour sensibiliser la tumeur aux rayonnements ionisants

Radiosensitizing effect of intratumoral interleukin-12 gene electrotransfer in murine sarcoma

Sedlar, Ales ; Kranjc, Simona ; Dolinsek, Tanja ; Cemazar, Maja ; Coer, Andrej ; Sersa, Gregor

BACKGROUND:Interleukin-12 (IL-12) based radiosensitization is an effective way of tumor treatment. Local cytokine production, without systemic shedding, might provide clinical benefit in radiation treatment of sarcomas. Therefore, the aim was to stimulate intratumoral IL-12 production by gene electrotransfer of plasmid coding for mouse IL-12 (mIL-12) into the tumors, in order to explore its radiosensitizing effect after single or multiple intratumoral gene electrotransfer.METHODS:Solid SA-1 [...]

Cet article présente les recommandations du réseau GARNET pour communiquer des résultats fortuits à des patients dont le génome a fait l'objet d'une analyse dans le cadre d'un essai clinique

Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET)

Bookman, Ebony ; Din-Lovinescu, Corina ; Worrall, Bradford ; Manolio, Teri ; Bennett, Siiri ; Laurie, Cathy ; Mirel, Daniel ; Doheny, Kimberly ; Anderson, Garnet ; Wehr, Kate ; Weinshilboum, Richard ; Chen, Donna ; for GARNET

Recommendations and guidance on how to handle the return of genetic results to patients have offered limited insight into how to approach incidental genetic findings in the context of clinical trials. This paper provides the Genomics and Randomized Trials Network (GARNET) recommendations on incidental genetic findings in the context of clinical trials, and discusses the ethical and practical issues considered in formulating our recommendations. There are arguments in support of as well as [...]