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https://www.readbyqxmd.com/read/28623775/cancer-immunotherapy-opportunities-and-challenges-in-the-rapidly-evolving-clinical-landscape
#1
REVIEW
Leisha A Emens, Paolo A Ascierto, Phillip K Darcy, Sandra Demaria, Alexander M M Eggermont, William L Redmond, Barbara Seliger, Francesco M Marincola
Cancer immunotherapy is now established as a powerful way to treat cancer. The recent clinical success of immune checkpoint blockade (antagonists of CTLA-4, PD-1 and PD-L1) highlights both the universal power of treating the immune system across tumour types and the unique features of cancer immunotherapy. Immune-related adverse events, atypical clinical response patterns, durable responses, and clear overall survival benefit distinguish cancer immunotherapy from cytotoxic cancer therapy. Combination immunotherapies that transform non-responders to responders are under rapid development...
June 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28592523/germline-cdkn2a-p16ink4a-mutations-contribute-to-genetic-determinism-of-sarcoma
#2
Fanélie Jouenne, Isaure Chauvot de Beauchene, Emeline Bollaert, Marie-Françoise Avril, Olivier Caron, Olivier Ingster, Axel Lecesne, Patrick Benusiglio, Philippe Terrier, Vincent Caumette, Daniel Pissaloux, Arnaud de la Fouchardière, Odile Cabaret, Birama N'Diaye, Amélie Velghe, Gaelle Bougeard, Graham J Mann, Serge Koscielny, Jennifer H Barrett, Mark Harland, Julia Newton-Bishop, Nelleke Gruis, Remco Van Doorn, Marion Gauthier-Villars, Gaelle Pierron, Dominique Stoppa-Lyonnet, Isabelle Coupier, Rosine Guimbaud, Capucine Delnatte, Jean-Yves Scoazec, Alexander M Eggermont, Jean Feunteun, Luba Tchertanov, Jean-Baptiste Demoulin, Thierry Frebourg, Brigitte Bressac-de Paillerets
BACKGROUND: Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS: We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma...
June 7, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28587095/comparative-study-of-lectin-domains-in-model-species-new-insights-into-evolutionary-dynamics
#3
Sofie Van Holle, Kristof De Schutter, Lore Eggermont, Mariya Tsaneva, Liuyi Dang, Els J M Van Damme
Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsisthaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica). The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST), hidden Markov models, and InterProScan analysis...
May 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28497279/aspiring-to-have-the-looks-of-a-celebrity-young-girls-engagement-in-appearance-management-behaviors
#4
Jolien Trekels, Steven Eggermont
Research suggests that sexualizing media messages are present in teen media and negatively affect young girls' body image. Yet, it is unknown whether exposure to teen television programs is associated with girls' engagement in appearance management behaviors. Two-wave longitudinal data among 785 girls (Mage = 11.65 years) were collected. Results show that teen television exposure was longitudinally related to appearance management, while the reverse relation was not supported. Approximately half of the girls indicated to manage their appearance to some extent, and 13- to 14-year-old girls were more likely to invest in their appearance than younger girls...
May 11, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28479096/comparing-the-therapeutic-potential-of-thermosensitive-liposomes-and-hyperthermia-in-two-distinct-subtypes-of-breast-cancer
#5
Wouter J M Lokerse, Michiel Bolkestein, Simone U Dalm, Alexander M M Eggermont, Marion de Jong, Holger Grüll, Gerben A Koning
Local drug delivery of Doxorubicin (Dox) with thermosensitive liposomes (TSL) and hyperthermia (HT) has shown preclinically to achieve high local drug concentrations with good therapeutic efficacy. Currently, this is clinically studied for treatment of chest wall recurrence of breast cancer, however with various outcomes. This study examines the potency of neoadjuvant TSL HT combination therapy in two orthotopic mouse models of human breast cancer, MDA-MB-231 and T-47D, which morphologically correlate to mesenchymal and epithelial phenotypes, respectively...
May 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28442455/use-of-fitness-and-nutrition-apps-associations-with-body-mass-index-snacking-and-drinking-habits-in-adolescents
#6
Nathalie De Cock, Jolien Vangeel, Carl Lachat, Kathleen Beullens, Leentje Vervoort, Lien Goossens, Lea Maes, Benedicte Deforche, Stefaan De Henauw, Caroline Braet, Steven Eggermont, Patrick Kolsteren, John Van Camp, Wendy Van Lippevelde
BACKGROUND: Efforts to improve snacking and drinking habits are needed to promote a healthy body mass index (BMI) in adolescents. Although commercial fitness and nutrition mobile phone apps are widely used, little is known regarding their potential to improve health behaviors, especially in adolescents. In addition, evidence on the mechanisms through which such fitness and nutrition apps influence behavior is lacking. OBJECTIVES: This study assessed whether the use of commercial fitness or nutrition apps was associated with a lower BMI and healthier snacking and drinking habits in adolescents...
April 25, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/28417534/cardiac-function-and-cognition-in-older-community-dwelling-cardiac-patients
#7
Laura H P Eggermont, Mohamed F A Aly, Pieter J Vuijk, Karin de Boer, Otto Kamp, Albert C van Rossum, Erik J A Scherder
BACKGROUND: Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. METHODS: An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification...
April 17, 2017: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
https://www.readbyqxmd.com/read/28414765/validation-of-full-field-optical-coherence-tomography-in-distinguishing-malignant-and-benign-tissue-in-resected-pancreatic-cancer-specimens
#8
Labrinus van Manen, Paulien L Stegehuis, Arantza Fariña-Sarasqueta, Lorraine M de Haan, Jeroen Eggermont, Bert A Bonsing, Hans Morreau, Boudewijn P F Lelieveldt, Cornelis J H van de Velde, Alexander L Vahrmeijer, Jouke Dijkstra, J Sven D Mieog
BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. The minority of patients can undergo curative-intended surgical therapy due to progressive disease stage at time of diagnosis. Nonetheless, tumor involvement of surgical margins is seen in up to 70% of resections, being a strong negative prognostic factor. Real-time intraoperative imaging modalities may aid surgeons to obtain tumor-free resection margins. Full-field optical coherence tomography (FF-OCT) is a promising diagnostic tool using high-resolution white-light interference microscopy without tissue processing...
2017: PloS One
https://www.readbyqxmd.com/read/28393131/controlling-t-cell-activation-with-synthetic-dendritic-cells-using-the-multivalency-effect
#9
Roel Hammink, Subhra Mandal, Loek J Eggermont, Marco Nooteboom, Peter H G M Willems, Jurjen Tel, Alan E Rowan, Carl G Figdor, Kerstin G Blank
Artificial antigen-presenting cells (aAPCs) have recently gained a lot of attention. They efficiently activate T cells and serve as powerful replacements for dendritic cells in cancer immunotherapy. Focusing on a specific class of polymer-based aAPCs, so-called synthetic dendritic cells (sDCs), we have investigated the importance of multivalent binding on T-cell activation. Using antibody-functionalized sDCs, we have tested the influence of polymer length and antibody density. Increasing the multivalent character of the antibody-functionalized polymer lowered the effective concentration required for T-cell activation...
March 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28382893/adding-a-reward-increases-the-reinforcing-value-of-fruit
#10
RANDOMIZED CONTROLLED TRIAL
Nathalie De Cock, Leentje Vervoort, Patrick Kolsteren, Lieven Huybregts, Wendy Van Lippevelde, Jolien Vangeel, Melissa Notebaert, Kathleen Beullens, Lien Goossens, Lea Maes, Benedicte Deforche, Caroline Braet, Steven Eggermont, John Van Camp, Carl Lachat
Adolescents' snack choices could be altered by increasing the reinforcing value (RV) of healthy snacks compared with unhealthy snacks. This study assessed whether the RV of fruit increased by linking it to a reward and if this increased RV was comparable with the RV of unhealthy snacks alone. Moderation effects of sex, hunger, BMI z-scores and sensitivity to reward were also explored. The RV of snacks was assessed in a sample of 165 adolescents (15·1 (sd 1·5) years, 39·4 % boys and 17·4 % overweight) using a computerised food reinforcement task...
February 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28368458/baseline-gut-microbiota-predicts-clinical-response-and-colitis-in-metastatic-melanoma-patients-treated-with-ipilimumab
#11
N Chaput, P Lepage, C Coutzac, E Soularue, K Le Roux, C Monot, L Boselli, E Routier, L Cassard, M Collins, T Vaysse, L Marthey, A Eggermont, V Asvatourian, E Lanoy, C Mateus, C Robert, F Carbonnel
Background: Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity. Patients and methods: Twenty-six patients with MM treated with ipilimumab were prospectively enrolled. Fecal microbiota composition was assessed using 16S rRNA gene sequencing at baseline and before each ipilimumab infusion...
June 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28365644/high-throughput-genomics-and-clinical-outcome-in-hard-to-treat-advanced-cancers-results-of-the-moscato-01-trial
#12
Christophe Massard, Stefan Michiels, Charles Ferté, Marie-Cécile Le Deley, Ludovic Lacroix, Antoine Hollebecque, Loic Verlingue, Ecaterina Ileana, Silvia Rosellini, Samy Ammari, Maud Ngo-Camus, Rastislav Bahleda, Anas Gazzah, Andrea Varga, Sophie Postel-Vinay, Yohann Loriot, Caroline Even, Ingrid Breuskin, Nathalie Auger, Bastien Job, Thierry De Baere, Frederic Deschamps, Philippe Vielh, Jean-Yves Scoazec, Vladimir Lazar, Catherine Richon, Vincent Ribrag, Eric Deutsch, Eric Angevin, Gilles Vassal, Alexander Eggermont, Fabrice André, Jean-Charles Soria
High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1...
June 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28334251/isolation-of-vibrionaceae-from-wild-blue-mussel-mytilus-edulis-adults-and-their-impact-on-blue-mussel-larviculture
#13
Mieke Eggermont, Peter Bossier, Gde Sasmita Julyantoro Pande, Vyshal Delahaut, Ali Md Rayhan, Nipa Gupta, Shikder Saiful Islam, Elsie Yumo, Nancy Nevejan, Patrick Sorgeloos, Bruno Gomez-Gil, Tom Defoirdt
The blue mussel (Mytilus edulis) is known as a robust bivalve species, although its larviculture appears to be highly susceptible to diseases. In this study, we isolated 17 strains from induced mortality events in healthy wild-caught blue mussel adults and demonstrated that they caused between 17% and 98% mortality in blue mussel larvae in a newly developed, highly controlled immersion challenge test model. Eight of the isolates belong to the Splendidus clade of vibrios, while the other isolates belong to the genus Photobacterium...
April 1, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28264934/structure-activity-relationship-of-thapsigargin-inhibition-on-the-purified-golgi-secretory-pathway-ca-2-mn-2-transport-atpase-spca1a
#14
Jialin Chen, Joren De Raeymaecker, Jannik Brøndsted Hovgaard, Susanne Smaardijk, Ilse Vandecaetsbeek, Frank Wuytack, Jesper Vuust Møller, Jan Eggermont, Marc De Maeyer, Søren Brøgger Christensen, Peter Vangheluwe
The Golgi/secretory pathway Ca(2+)/Mn(2+)-transport ATPase (SPCA1a) is implicated in breast cancer and Hailey-Hailey disease. Here, we purified recombinant human SPCA1a from Saccharomyces cerevisiae and measured Ca(2+)-dependent ATPase activity following reconstitution in proteoliposomes. The purified SPCA1a displays a higher apparent Ca(2+) affinity and a lower maximal turnover rate than the purified sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1a). The lipids cholesteryl hemisuccinate, linoleamide/oleamide, and phosphatidylethanolamine inhibit and phosphatidic acid and sphingomyelin enhance SPCA1a activity...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28262276/long-term-results-of-ultrasound-guided-fine-needle-aspiration-cytology-in-conjunction-with-sentinel-node-biopsy-support-step-wise-approach-in-melanoma
#15
C M C Oude Ophuis, C Verhoef, D J Grünhagen, P Siegel, A Schoengen, J Röwert-Huber, A M M Eggermont, C A Voit, A C J van Akkooi
BACKGROUND: US-FNAC is a common diagnostic tool in the work-up of many cancers. Results in melanoma were initially poor (sensitivity 20-40%). Introduction of the Berlin Morphology criteria has shown potential improvement up to 65-80% in selected patients. AIM: This cohort study evaluates the long-term survival outcome of melanoma patients undergoing Ultrasound (US) guided Fine Needle Aspiration Cytology (FNAC) prior to sentinel node biopsy (SNB) or direct lymphadenectomy...
February 21, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28218385/timing-of-completion-lymphadenectomy-after-positive-sentinel-node-biopsy-in-patients-with-melanoma
#16
MULTICENTER STUDY
C M C Oude Ophuis, A C J van Akkooi, P Rutkowski, W E M Powell, C Robert, A Testori, B L van Leeuwen, P Siegel, A M M Eggermont, C Verhoef, D J Grünhagen
BACKGROUND: Nodal staging with sentinel node biopsy (SNB) and completion lymph node dissection (CLND) provides prognostic information to patients with melanoma and their physicians. It is not known whether the timing of CLND is associated with survival outcome and/or CLND tumour load. This study investigated whether CLND timing is associated with CLND tumour load, disease-free survival (DFS) and/or melanoma-specific survival (MSS). METHODS: A retrospective cohort of patients with SNB-positive melanoma from nine European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group centres undergoing surgery between 1993 and 2009 were examined...
May 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28197362/prognostic-impact-of-the-expression-of-ncr1-and-ncr3-nk-cell-receptors-and-pd-l1-on-advanced-non-small-cell-lung-cancer
#17
Laetitia Fend, Sylvie Rusakiewicz, Julien Adam, Bérangère Bastien, Anne Caignard, Meriem Messaoudene, Christina Iribarren, Isabelle Cremer, Aurélien Marabelle, Christophe Borg, Michaela Semeraro, Luc Barraud, Jean-Marc Limacher, Alexander Eggermont, Guido Kroemer, Laurence Zitvogel
The putative contribution of natural killer (NK) cells to immunosurveillance in non-small cell lung cancer (NSCLC) has been an ongoing conundrum. Here, we used a readily standardizable quantitative real time polymerase chain reaction (qRT-PCR) to measure the expression of NK cell receptors in total peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV), patients with gastrointestinal stromal tumors (GIST), neuroblastoma (NB), melanoma or NSCLC. We quantified NCR1 (which codes for NKp46) and NCR3 (which codes for NKp30), as well as that of three NCR3 splice variants (which give rise to immunostimulatory NKp30A and NKp30B, as well as to immunosuppressive NKp30C)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197361/nkp30-isoforms-and-nkp30-ligands-are-predictive-biomarkers-of-response-to-imatinib-mesylate-in-metastatic-gist-patients
#18
Sylvie Rusakiewicz, Aurélie Perier, Michaela Semeraro, Jonathan M Pitt, Elke Pogge von Strandmann, Katrin S Reiners, Sandrine Aspeslagh, Christelle Pipéroglou, Frédéric Vély, Alexandre Ivagnes, Sarah Jegou, Niels Halama, Loic Chaigneau, Pierre Validire, Christos Christidis, Thierry Perniceni, Bruno Landi, Anne Berger, Nicolas Isambert, Julien Domont, Sylvie Bonvalot, Philippe Terrier, Julien Adam, Jean-Michel Coindre, Jean-François Emile, Vichnou Poirier-Colame, Kariman Chaba, Benedita Rocha, Anne Caignard, Antoine Toubert, David Enot, Joachim Koch, Aurélien Marabelle, Marion Lambert, Sophie Caillat-Zucman, Serge Leyvraz, Christian Auclair, Eric Vivier, Alexander Eggermont, Christophe Borg, Jean-Yves Blay, Axel Le Cesne, Olivier Mir, Laurence Zitvogel
Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28174524/ups-and-downs-in-75-years-of-electrocochleography
#19
REVIEW
Jos J Eggermont
Before 1964, electrocochleography (ECochG) was a surgical procedure carried out in the operating theatre. Currently, the newest application is also an intra-operative one, often carried out in conjunction with cochlear implant surgery. Starting in 1967, the recording methods became either minimal- or not-invasive, i.e., trans-tympanic (TT) or extra tympanic (ET), and included extensive studies of the arguments pro and con. I will review several valuable applications of ECochG, from a historical point of view, but covering all 75 years if applicable...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28162999/health-related-quality-of-life-with-adjuvant-ipilimumab-versus-placebo-after-complete-resection-of-high-risk-stage-iii-melanoma-eortc-18071-secondary-outcomes-of-a-multinational-randomised-double-blind-phase-3-trial
#20
RANDOMIZED CONTROLLED TRIAL
Corneel Coens, Stefan Suciu, Vanna Chiarion-Sileni, Jean-Jacques Grob, Reinhard Dummer, Jedd D Wolchok, Henrik Schmidt, Omid Hamid, Caroline Robert, Paolo A Ascierto, Jon M Richards, Celeste Lebbé, Virginia Ferraresi, Michael Smylie, Jeffrey S Weber, Michele Maio, Andrew Bottomley, Srividya Kotapati, Veerle de Pril, Alessandro Testori, Alexander M M Eggermont
BACKGROUND: The EORTC 18071 phase 3 trial compared adjuvant ipilimumab with placebo in patients with stage III melanoma. The primary endpoint, recurrence-free survival, was significantly longer in the ipilimumab group than in the placebo group. Investigator-reported toxic effects of ipilimumab consisted mainly of skin, gastrointestinal, endocrine, and hepatic immune-related adverse events. Adjuvant treatment with ipilimumab in this setting was approved in October, 2014, by the US Food and Drug Administration based on the results of the primary outcome of this trial...
March 2017: Lancet Oncology
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