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Molecular tumour board

Sebastian Schmid, Bettina Jungwirth, Verena Gehlert, Manfred Blobner, Gerhard Schneider, Stephan Kratzer, Kristine Kellermann, Gerhard Rammes
BACKGROUND: The intracerebroventricular injection of beta-amyloid (Aβ) in mice allows the investigation of acute effects on cognitive function and cellular pathology. The aim of this investigation was to further characterize the time course of Aβ-induced cognitive and behavioural changes and to detect potential molecular mechanisms. METHODS: Cannulas were implanted in the lateral cerebral ventricle. 14days after surgery the mice were injected with Aβ1-42 or phosphate buffered saline (PBS)...
May 1, 2017: Behavioural Brain Research
Barbara C Worst, Cornelis M van Tilburg, Gnana Prakash Balasubramanian, Petra Fiesel, Ruth Witt, Angelika Freitag, Miream Boudalil, Christopher Previti, Stephan Wolf, Sabine Schmidt, Sasithorn Chotewutmontri, Melanie Bewerunge-Hudler, Matthias Schick, Matthias Schlesner, Barbara Hutter, Lenka Taylor, Tobias Borst, Christian Sutter, Claus R Bartram, Till Milde, Elke Pfaff, Andreas E Kulozik, Arend von Stackelberg, Roland Meisel, Arndt Borkhardt, Dirk Reinhardt, Jan-Henning Klusmann, Gudrun Fleischhack, Stephan Tippelt, Uta Dirksen, Heribert Jürgens, Christof M Kramm, Andre O von Bueren, Frank Westermann, Matthias Fischer, Birgit Burkhardt, Wilhelm Wößmann, Michaela Nathrath, Stefan S Bielack, Michael C Frühwald, Simone Fulda, Thomas Klingebiel, Ewa Koscielniak, Matthias Schwab, Roman Tremmel, Pablo Hernáiz Driever, Johannes H Schulte, Benedikt Brors, Andreas von Deimling, Peter Lichter, Angelika Eggert, David Capper, Stefan M Pfister, David T W Jones, Olaf Witt
The 'Individualized Therapy for Relapsed Malignancies in Childhood' (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9)...
September 2016: European Journal of Cancer
Valentin Zumstein, Fabrizio Vinzens, Andreas Zettl, Karl Heinimann, Dieter Koeberle, Markus von Flüe, Martin Bolli
BACKGROUND: Germline mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause autosomal dominantly inherited Lynch syndrome. Lynch syndrome patients and their families benefit from life-saving intensive cancer surveillance. Approximately one in 30 colorectal cancers arises in the setting of Lynch syndrome. OBJECTIVE: The aim of this study was to assess the detection rate of Lynch syndrome at our institution after introduction of systematic immunohistochemical screening for MMR deficiency in colorectal cancers from 2011 to 2015...
2016: Swiss Medical Weekly
Antoine Italiano, Ilaria Di Mauro, Jocelyn Rapp, Gaëlle Pierron, Nathalie Auger, Laurent Alberti, Frédéric Chibon, Fabienne Escande, Anne-Claire Voegeli, Jean-Pierre Ghnassia, Frédérique Keslair, Marick Laé, Dominique Ranchère-Vince, Philippe Terrier, Sandrine Baffert, Jean-Michel Coindre, Florence Pedeutour
BACKGROUND: Advances in molecular genetics of sarcoma have enabled the identification of type-specific aberrations. We aimed to assess the clinical effect of systematic implementation of molecular assays to improve sarcoma misdiagnosis. METHODS: In this multicentre, observational study, we recruited patients from 32 centres of the French Sarcoma Group/Reference Network in Pathology of Sarcomas. Eligibility criteria included: biopsy or surgical resection; suspicion of: dermatofibrosarcoma protuberans (cohort 1), dedifferentiated liposarcoma (cohort 2), Ewing's sarcoma family of tumours (cohort 3), synovial sarcoma (cohort 4), alveolar rhabdomyosarcoma (cohort 5), and myxoid or round cell liposarcoma (cohort 6); review by one sarcoma-expert pathologist; availability of frozen material (except for cohort 1 of patients with dermatofibrosarcoma protuberans because anti-CD34 immunohistochemistry is performed on paraffin-embedded tissue); and patient information...
April 2016: Lancet Oncology
M Giefing, M Wierzbicka, K Szyfter, J C Brenner, B J Braakhuis, R H Brakenhoff, C R Bradford, J A Sorensen, A Rinaldo, J P Rodrigo, R P Takes, A Ferlito
Personalised medicine tumour boards, which leverage genomic data to improve clinical management, are becoming standard for the treatment of many cancers. This paper is designed as a primer to assist clinicians treating head and neck squamous cell carcinoma (HNSCC) patients with an understanding of the discovery and functional impact of recurrent genetic lesions that are likely to influence the management of this disease in the near future. This manuscript integrates genetic data from publicly available array comparative genome hybridization (aCGH) and next-generation sequencing genetics databases to identify the most common molecular alterations in HNSCC...
March 2016: European Journal of Cancer
Manfred Dietel, Lukas Bubendorf, Anne-Marie C Dingemans, Christophe Dooms, Göran Elmberger, Rosa Calero García, Keith M Kerr, Eric Lim, Fernando López-Ríos, Erik Thunnissen, Paul E Van Schil, Maximilian von Laffert
BACKGROUND: There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. METHODS: Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned...
February 2016: Thorax
Arturo Loaiza-Bonilla, Erica Clayton, Emma Furth, Mark O'Hara, Jennifer Morrissette
This is the case of a 47-year-old woman diagnosed with chemotherapy and radiation-refractory BRAF V600E mutant, poorly differentiated intrahepatic cholangiocarcinoma (ICC), with multiple metastatic lesions within the liver, lungs, pleura, and bone, stage IV. Discussion of her malignancy's next-generation sequencing genomic information at a multidisciplinary molecular tumour board took place. The patient was considered a suitable candidate for dual BRAF and MEK inhibition, with the intent to prolong her survival and optimize the quality of life...
2014: Ecancermedicalscience
C Le Tourneau, X Paoletti, N Servant, I Bièche, D Gentien, T Rio Frio, A Vincent-Salomon, V Servois, J Romejon, O Mariani, V Bernard, P Huppe, G Pierron, F Mulot, C Callens, J Wong, C Mauborgne, E Rouleau, C Reyes, E Henry, Q Leroy, P Gestraud, P La Rosa, L Escalup, E Mitry, O Trédan, J-P Delord, M Campone, A Goncalves, N Isambert, C Gavoille, M Kamal
BACKGROUND: The SHIVA trial is a multicentric randomised proof-of-concept phase II trial comparing molecularly targeted therapy based on tumour molecular profiling vs conventional therapy in patients with any type of refractory cancer. RESULTS of the feasibility study on the first 100 enrolled patients are presented. METHODS: Adult patients with any type of metastatic cancer who failed standard therapy were eligible for the study. The molecular profile was performed on a mandatory biopsy, and included mutations and gene copy number alteration analyses using high-throughput technologies, as well as the determination of oestrogen, progesterone, and androgen receptors by immunohistochemistry (IHC)...
July 8, 2014: British Journal of Cancer
I Gockel, F Watzka, T J Musholt, H Lang
Neuroendocrine tumours (NET) of the stomach have increasingly entered into the focus of attention recently by endocrinologists as well as by surgeons on account of new findings on their biological background and their clinical relevance. The discriminating pathogenesis and the basically different biological behaviours of neuroendocrine tumours of the stomach require a differentiated therapeutical treatment for the different sub-types. The differential diagnostic clarification of the basic pathomechanism is therefore of decisive importance...
June 2010: Zentralblatt Für Chirurgie
Darren R Hodgson, Robert Wellings, Maria C M Orr, Rose McCormack, Michael Malone, Ruth E Board, Mireille V Cantarini
Molecular characterization of tumour material will become increasingly important in selecting patients for clinical trials and offering appropriate treatment for patients in clinical practice. Recent advances in the field have indicated that the molecular characteristics of a tumour can be determined from circulating tumour cells and circulating tumour DNA; thus, a simple blood sample could provide these data in a simple, convenient and efficient manner. This article discusses progress towards guiding treatment decisions through measuring tumour-derived factors in the circulation...
February 2010: Drug Discovery Today
(no author information available yet)
Introgen and its wholly owned European subsidiary Gendux AB are developing an adenoviral p53 gene therapy as a treatment for cancer in the US and Europe, respectively. Phase III trials in patients with head and neck cancer are ongoing, and a number of clinical trials in other cancer indications have been completed. INGN 201 is being reviewed by the EMEA for approval in Li-Fraumeni syndrome (LFS) under the provisions of exceptional circumstance; the therapy is available on a compassionate use basis to eligible LFS cancer patients under a protocol authorised by the US FDA...
2007: Drugs in R&D
D K Scott, J R Board, X Lu, A D J Pearson, R M Kenyon, J Lunec
Amplification of the MYCN oncogene in neuroblastoma is associated with poor prognosis. The amplified unit of DNA can be up to 1 Mb in size and so could contain additional genes which affect tumour phenotype. The neuroblastoma amplified gene (NAG) gene was initially located 400 kb telomeric to MYCN at 2p24 and reported to be co-amplified in 5/8 (63%) cell lines and 9/13 (70%) tumours. The sequence of a 4.5 kb transcript was proposed from the analysis of overlapping cDNA clones. However, our Northern blot hybridisation experiments indicate that the main RNA species expressed in neuroblastoma is 7-8 kb in size...
March 27, 2003: Gene
G Chenevix-Trench, J Young, M Coggan, P Board
The M1 member of the Mu subclass of glutathione S-transferase (GSTM1) is only expressed in about 50% of individuals. In contrast, GSTT1, a member of the theta class which has been recently shown to be polymorphic, is expressed in 85% of Australian individuals. Previous studies have shown a significant excess of homozygous null GSTM1 genotypes among individuals with colorectal cancer, particularly those with proximal tumours. This suggests that GSTM1 plays a role in susceptibility to this neoplasm. In this study of 132 individuals with colorectal cancer and 200 controls, no significant excess of GSTM1 homozygous null genotypes was found among colorectal cancer patients with either a proximal or distal tumour...
July 1995: Carcinogenesis
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