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Molecular tumour board

Liran Domachevsky, Natalia Goldberg, Hanna Bernstine, Meital Nidam, David Groshar
OBJECTIVES: To quantitatively characterize clinically significant intra-prostatic cancer (IPC) by prostate-specific membrane antigen (PSMA) expression and cell density on PSMA-11 positron emission tomography/magnetic resonance (PET/MR). METHODS: Retrospective study approved by the institutional review board with informed written consent obtained. Patients with a solitary, biopsy-proven prostate cancer, Gleason score (GS) ≥7, presenting for initial evaluation by PET/computerised tomography (PET/CT), underwent early prostate PET/MR immediately after PSMA-11 tracer injection...
May 30, 2018: European Radiology
J Hofmanová, J Slávik, Z Tylichová, P Ovesná, J Bouchal, Z Kolář, J Ehrmann, M Levková, M Machala, J Vondráček, A Kozubík
BACKGROUNDS: Colon cancer development is often characterized by abnormalities in lipid synthesis and metabolism, which may influence energetic balance, structure and function of biological membranes, or production of specific mediators and cell signalling. The changes in lipid profile and metabolism (lipidome) may significantly affect cell behaviour and response to therapy. Permanent epithelial cell lines at various stages of cancer development are used for better understanding of this topic on cellular and molecular levels...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Belinda Lee, Ben Tran, Arthur L Hsu, Graham R Taylor, Stephen B Fox, Andrew Fellowes, Renata Marquis, Jennifer Mooi, Jayesh Desai, Ken Doig, Paul Ekert, Clara Gaff, Dishan Herath, Anne Hamilton, Paul James, Andrew Roberts, Ray Snyder, Paul Waring, Grant McArthur
BACKGROUND: Technology has progressed from single gene panel to large-scale genomic sequencing. This is raising expectations from clinicians and patients alike. The utility and performance of this technology in a clinical setting needs to be evaluated. AIM: This pilot study investigated the feasibility of using exome-scale sequencing (ESS) to identify molecular drivers within cancers in real-time for Precision oncology in the clinic. METHODS: Between March 2014 and March 2015, the Victorian Comprehensive Cancer Centre Alliance explored the feasibility and utility of ESS in a pilot study...
April 1, 2018: Internal Medicine Journal
Sheela Joseph, Rajinikanth Janakiraman, Geeta Chacko, Rama Jayaraj, Mahiban Thomas, Meera Thomas, Sramana Mukhopadhyay
OBJECTIVES: Treatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates of recurrence. Incomplete surgical removal of the tumour, attributed to lack of reliable methods to delineate the surgical margins, is a major cause of disease recurrence. The predictability of recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM) in mucosal HNSCC study aims to redefine margin status by identifying the true extent of the tumour at the molecular level by performing IHC with molecular markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on the surgical margins and test the use of Lugol's iodine and fluorescence visualisation prior to the wide local excision...
October 15, 2017: BMJ Open
Su Hyun Lee, Jung Min Chang, Sung Ui Shin, A Jung Chu, Ann Yi, Nariya Cho, Woo Kyung Moon
OBJECTIVE: To evaluate imaging features of breast cancers on digital breast tomosynthesis (DBT) according to molecular subtype and to determine whether the molecular subtype affects breast cancer detection on DBT. METHODS: This was an institutional review board--approved study with a waiver of informed consent. DBT findings of 288 invasive breast cancers were reviewed according to Breast Imaging Reporting and Data System lexicon. Detectability of breast cancer was quantified by the number of readers (0-3) who correctly detected the cancer in an independent blinded review...
December 2017: British Journal of Radiology
Anne Hansen Ree, Hege G Russnes, Daniel Heinrich, Svein Dueland, Kjetil Boye, Vigdis Nygaard, Laxmi Silwal-Pandit, Olga Østrup, Eivind Hovig, Vegard Nygaard, Einar A Rødland, Sigve Nakken, Janne T Øien, Christin Johansen, Inger R Bergheim, Veronica Skarpeteig, Menaka Sathermugathevan, Torill Sauer, Marius Lund-Iversen, Klaus Beiske, Salah Nasser, Lars Julsrud, Claudius H Reisse, Espen A Ruud, Vivi Ann Flørenes, Kirsten T Hagene, Eline Aas, Hilde Lurås, Siv Johnsen-Soriano, Gry A Geitvik, Ole Christian Lingjærde, Anne-Lise Børresen-Dale, Gunhild M Mælandsmo, Kjersti Flatmark
OBJECTIVE: Through the conduct of an individual-based intervention study, the main purpose of this project was to build and evaluate the required infrastructure that may enable routine practice of precision cancer medicine in the public health services of Norway, including modelling of costs. METHODS: An eligible patient had end-stage metastatic disease from a solid tumour. Metastatic tissue was analysed by DNA sequencing, using a 50-gene panel and a study-generated pipeline for analysis of sequence data, supplemented with fluorescence in situ hybridisation to cover relevant biomarkers...
2017: ESMO Open
W J Choi, J H Cha, H H Kim, H J Shin, E Y Chae, K H Jung, J-H Ahn, S-B Kim, B H Son, S H Ahn
AIMS: To investigate whether preoperative magnetic resonance imaging (MRI) in patients with primary breast cancer is predictive of disease-free (DFS) and overall survival and to determine the prognostic factors indicating survival. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. From 2009 to 2010, 828 women with primary breast cancer and preoperative MRI were matched with 1613 women without such imaging...
October 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
Andreas Mock, Suzanne Murphy, James Morris, Francesco Marass, Nitzan Rosenfeld, Charlie Massie
BACKGROUND: An increasing number of precision oncology programmes are being launched world-wide. To support this development, we present the Cancer Variant Explorer (CVE), an R package with an interactive Shiny web browser interface. RESULTS: Leveraging Oncotator and the Drug Gene Interaction Database, CVE offers exploration of variants within single or multiple tumour exomes to identify drivers, resistance mechanisms and to assess druggability. We present example applications including the analysis of an individual patient and a cohort-wide study, and provide a first extension of CVE by adding a tumour-specific co-expression network...
May 25, 2017: BMC Medical Genomics
V Brychtová, R Šefr, R Hrstka, P Vídeňská, B Bencsiková, B Hanáková, L Zdražilová Dubská, R Nenutil, E Budinská
BACKGROUND: Colorectal carcinoma (CRC) is third most common cancer worldwide with very heterogenous character. In most cases, it is caused by sporadic events leading to disruption of epithelial cells of the colon. The minority evolves from germline mutations associated with hereditary cancer syndromes. Mechanisms leading to mutations of oncogenes, tumour suppressors and genes of DNA repair mechanisms include: 1. chromosomal instability, 2. microsatellite instability and 3. CpG island methylator phenotype...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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
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