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https://www.readbyqxmd.com/read/28339824/a-phase-i-trial-of-the-mek-inhibitor-selumetinib-azd6244-in-pediatric-patients-with-recurrent-or-refractory-low-grade-glioma-a-pediatric-brain-tumor-consortium-pbtc-study
#1
Anuradha Banerjee, Regina I Jakacki, Arzu Onar-Thomas, Shengjie Wu, Theodore Nicolaides, Tina Young Poussaint, Jason Fangusaro, Joanna Phillips, Arie Perry, David Turner, Michael Prados, Roger J Packer, Ibrahim Qaddoumi, Sridharan Gururangan, Ian F Pollack, Stewart Goldman, Lawrence A Doyle, Clinton F Stewart, James M Boyett, Larry E Kun, Maryam Fouladi
Background.: Activation of the mitogen-activated protein kinase pathway is important for growth of pediatric low-grade gliomas (LGGs). The aim of this study was to determine the recommended phase II dose (RP2D) and the dose-limiting toxicities (DLTs) of the MEK inhibitor selumetinib in children with progressive LGG. Methods.: Selumetinib was administered orally starting at 33 mg/m2/dose b.i.d., using the modified continual reassessment method. Pharmacokinetic analysis was performed during the first course...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339700/a-clinical-perspective-on-the-2016-who-brain-tumor-classification-and-routine-molecular-diagnostics
#2
Martin J van den Bent, Michael Weller, Patrick Y Wen, Johan M Kros, Ken Aldape, Susan Chang
The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classification, which is now for adult diffuse glioma centered around isocitrate dehydrogenase (IDH) and 1p/19q diagnostics. This revised classification is reviewed with a focus on adult brain tumors, and includes a recommendation of genes of which routine testing is clinically useful...
February 21, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#3
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28333239/small-bowel-carcinomas-in-coeliac-or-crohn-s-disease-clinico-pathological-molecular-and-prognostic-features-a-study-from-the-small-bowel-cancer-italian-consortium
#4
Alessandro Vanoli, Antonio Di Sabatino, Daniela Furlan, Catherine Klersy, Federica Grillo, Roberto Fiocca, Claudia Mescoli, Massimo Rugge, Gabriella Nesi, Paolo Fociani, Gianluca Sampietro, Sandro Ardizzone, Ombretta Luinetti, Antonio Calabrò, Francesco Tonelli, Umberto Volta, Donatella Santini, Giacomo Caio, Paolo Giuffrida, Luca Elli, Stefano Ferrero, Giovanni Latella, Antonio Ciardi, Roberto Caronna, Gaspare Solina, Aroldo Rizzo, Carolina Ciacci, Francesco P D'Armiento, Marianna Salemme, Vincenzo Villanacci, Renato Cannizzaro, Vincenzo Canzonieri, Luca Reggiani Bonetti, Livia Biancone, Giovanni Monteleone, Augusto Orlandi, Giuseppe Santeusanio, Maria C Macciomei, Renata D'Incà, Vittorio Perfetti, Giancarlo Sandri, Marco Silano, Ada M Florena, Antonino G Giannone, Claudio Papi, Luigi Coppola, Paolo Usai, Antonio Maccioni, Marco Astegiano, Paola Migliora, Rachele Manca, Michele Martino, Davide Trapani, Roberta Cerutti, Paola Alberizzi, Roberta Riboni, Fausto Sessa, Marco Paulli, Enrico Solcia, Gino R Corazza
Background and Aims.: An increased risk of small bowel carcinoma (SBC) has been reported in coeliac disease (CD) and Crohn's disease (CrD). We explored clinico-pathologic, molecular and prognostic features of CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) in comparison with sporadic SBC (spo-SBC). Methods.: Seventy-six patients undergoing surgical resection for non-familial SBC (26 CD-SBC, 25 CrD-SBC, 25 spo-SBC) were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability (MSI) and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations...
February 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332309/effects-of-mir-145-5p-through-nras-on-the-cell-proliferation-apoptosis-migration-and-invasion-in-melanoma-by-inhibiting-mapk-and-pi3k-akt-pathways
#5
Sha Liu, Guozhen Gao, Dexiong Yan, Xiangjun Chen, Xingwei Yao, Shuzhong Guo, Guirong Li, Yu Zhao
We aimed to detect the effects of miR-145-5p on the cell proliferation, apoptosis, migration, and invasion in NRAS-mutant, BRAF-mutant, and wild-type melanoma cells, in order to figure out the potential mechanisms and provide a novel therapeutic target of melanoma. RT-qPCR and western blot were used to detect the expression of miR-145-5p and NRAS in melanoma tumor tissues and cells, respectively. Luciferase assay was performed to determine whether miR-145-5p directly targeted NRAS. After transfecting miR-145-5p mimics, miR-145-5p inhibitors, NRAS cDNA and NRAS siRNA into CHL-1, VMM917 and SK-mel-28 cells, functional assays were used to detect the proliferation, apoptosis, invasion and migration, including MTT, flow cytometry, Transwell and wound healing assays...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28331529/detection-of-braf-mutation-in-the-cytocentrifugation-supernatant-fluid-from-fine-needle-aspiration-of-thyroid-lesions-may-enhance-the-diagnostic-yield
#6
Ashley E Brown, Khin Sandar Lim, George Corpus, Martha T Hustek, Tien Anh N Tran, Chung-Che Chang
OBJECTIVE: BRAF mutations using cellular DNA from fine-needle aspiration (FNA) specimens are commonly used to support the diagnosis of papillary thyroid carcinoma (PTC). The goal of this study was to preliminarily evaluate the diagnostic utility of detecting BRAF mutations in the routinely discarded FNA specimen supernatant fluid. MATERIALS AND METHODS: Seventy-eight FNAs of thyroid lesions were evaluated for BRAF mutations using both cellular and supernatant DNA...
2017: CytoJournal
https://www.readbyqxmd.com/read/28329426/clinicopathological-characteristics-including-braf-v600e-mutation-status-and-pet-ct-findings-in-papillary-thyroid-carcinoma
#7
Eun Kyoung Choi, Ari Chong, Jung-Min Ha, Chan Kwon Jung, Joo Hyun O, Sung Hoon Kim
OBJECTIVE: We assessed the associations between FDG uptake in primary papillary thyroid carcinomas (PTCs) and clinicopathological features, including the BRAF V600E mutation, using quantitative and qualitative analyses of preoperative PET/CT data. DESIGN AND PATIENTS: This was a retrospective review of 106 patients with PTC who underwent PET/CT scans between February 2009 and January 2011 before undergoing total thyroidectomy. Data collected from surgical specimens were compared with FDG uptake in the primary tumor using quantitative and qualitative analyses of preoperative PET/CT data...
March 22, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28329154/brugada-syndrome-induced-by-braf-and-mek-inhibitors-in-a-melanoma-patient
#8
Charlée Nardin, Morgane Colas, Marc Badoz, Blandine Roche-Kubler, Nicolas Meneveau, Eve Puzenat, François Aubin
No abstract text is available yet for this article.
March 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28327908/predicted-vitamin-d-status-and-colon-cancer-recurrence-and-mortality-in-calgb-89803-alliance
#9
M A Fuchs, C Yuan, K Sato, D Niedzwiecki, X Ye, L B Saltz, R J Mayer, R B Mowat, R Whittom, A Hantel, A Benson, D Atienza, M Messino, H Kindler, A Venook, F Innocenti, R S Warren, M M Bertagnolli, S Ogino, E L Giovannucci, E Horvath, J A Meyerhardt, K Ng
Background: HASH(0x4733590) Observational studies suggest that higher levels of 25-hydroxyvitamin D 3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. Patients and methods: HASH(0x4736378) We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1,016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803)...
March 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28326956/clinical-pathologic-and-genetic-features-of-wilms-tumors-with-wtx-gene-mutation
#10
Sanda Alexandrescu, Sara Akhavanfard, Marian H Harris, Sara O Vargas
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28325827/sessile-serrated-polyps-and-colon-cancer-prevention
#11
Shahrooz Rashtak, Rafaela Rego, Seth R Sweetser, Frank A Sinicrope
Evidence suggests that up to one fifth of colorectal carcinomas (CRC) develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic CRCs with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps...
March 21, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28325255/mucosal-melanoma-of-the-head-and-neck
#12
REVIEW
Paolo Antonio Ascierto, Remo Accorona, Gerardo Botti, Davide Farina, Piero Fossati, Gemma Gatta, Helen Gogas, Davide Lombardi, Roberto Maroldi, Piero Nicolai, Marco Ravanelli, Vito Vanella
Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323937/tert-braf-and-nras-in-primary-thyroid-cancer-and-metastatic-disease
#13
Miguel Melo, Adriana Gaspar da Rocha, Rui Batista, João Vinagre, Maria João Martins, Gracinda Costa, Cristina Ribeiro, Francisco Carrilho, Valeriano Leite, Cláudia Lobo, José Manuel Cameselle-Teijeiro, Bruno Cavadas, Luísa Pereira, Manuel Sobrinho-Simões, Paula Soares
Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNM) and distant metastases. Design and patients: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTC) (n=180), including 196 LNM and 56 distant metastases...
March 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323782/controversies-in-intrapatient-melanoma-brafv600e-mutation-status
#14
Erica Riveiro-Falkenbach, Angel Santos-Briz, Juan J Ríos-Martín, José L Rodríguez-Peralto
Therapies targeting the BRAF oncogene have improved the overall and disease-free survival of patients with advanced melanomas. An unresolved issue in clinical practice is the existence (or not) of BRAF-mutated and BRAF-nonmutated tumors in individual patients (intrapatient BRAF mutation heterogeneity), which may serve as a mechanism of resistance to BRAF inhibitors or lead to diagnostic problems. Different research groups have reported differing results after analyzing the BRAF mutation statuses of multiple melanoma tumors...
April 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#15
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10 %. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
March 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28320730/prediction-of-the-transporter-mediated-drug-drug-interaction-potential-of-dabrafenib-and-its-major-circulating-metabolites
#16
Harma Ellens, Marta Johnson, Sarah K Lawrence, Cory A Watson, Liangfu Chen, Lauren E Richards-Peterson
The BRAF inhibitor dabrafenib was recently approved for the treatment of certain BRAF V600 mutation-positive tumors, either alone or in combination therapy with the MEK inhibitor trametinib. This article presents the dabrafenib transporter-mediated drug-drug interaction risk assessment, which is currently an important part of drug development, regulatory submission and drug registration. Dabrafenib and its major circulating metabolites (hydroxy-, carboxy- and desmethyl-dabrafenib) were investigated as inhibitors of the clinically relevant transporters Pgp, BCRP, OATP1B1, OATP1B3, OCT2, OAT1 and OAT3...
March 20, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28319896/a-dynamic-sandwich-assay-on-magnetic-beads-for-selective-detection-of-single-nucleotide-mutations-at-room-temperature
#17
Junxiu Wang, Guoliang Xiong, Liang Ma, Shihui Wang, Xu Zhou, Lei Wang, Lehui Xiao, Xin Su, Changyuan Yu
Single-nucleotide mutation (SNM) has proven to be associated with a variety of human diseases. Development of reliable methods for the detection of SNM is crucial for molecular diagnosis and personalized medicine. The sandwich assays are widely used tools for detecting nucleic acid biomarkers due to their low cost and rapid signaling. However, the poor hybridization specificity of signal probe at room temperature hampers the discrimination of mutant and wild type. Here, we demonstrate a dynamic sandwich assay on magnetic beads for SNM detection based on the transient binding between signal probe and target...
March 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28317244/juxtaglomerular-cell-tumor-clinical-and-immunohistochemical-features
#18
Fen Wang, Chuan Shi, Yunying Cui, Chunyan Li, Anli Tong
Juxtaglomerular cell tumor (JGCT) is a rare tumor, with approximately 100 cases reported in the literature. The authors respectively studied the clinical data of 11 patients diagnosed with JGCT in Peking Union Medical College Hospital from 2004 to 2014, and investigated the immunohistochemical profiles in 10 tumors. Nine of the 11 patients were diagnosed before the age of 40 years. Hypertension was present in all patients, while hypokalemia occurred in seven of 11 patients. Computed tomography detected JGCTs with a sensitivity of 100%...
March 20, 2017: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/28315738/pulmonary-sarcomatoid-carcinomas-commonly-harbor-either-potentially-targetable-genomic-alterations-or-high-tumor-mutational-burden-as-observed-by-comprehensive-genomic-profiling
#19
Alexa B Schrock, Shuyu D Li, Garrett M Frampton, James Suh, Eduardo Braun, Ranee Mehra, Steven Buck, Jose A Bufill, Nir Peled, Nagla Abdel Karim, Cynthia Hsieh, Manuel Doria, James Knost, Rong Chen, Sai-Hong Ignatius Ou, Jeffrey S Ross, Philip J Stephens, Paul Fishkin, Vincent A Miller, Siraj M Ali, Balazs Halmos, Jane J Liu
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered due to limited and inconsistent molecular characterization. METHODS: Hybrid-capture based comprehensive genomic profiling (CGP) was performed on DNA from 15,867 FFPE NSCLCs including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1...
March 15, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28314770/cribriform-morular-variant-of-papillary-thyroid-carcinoma-a-distinctive-type-of-thyroid-cancer
#20
REVIEW
Alfred King-Yin Lam, Nassim Saremi
The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over half of the patients with CMV-PTC had familial adenomatous polyposis (FAP). CMV-PTC presented before the colonic manifestations in approximately half of the patients with FAP. Patients with FAP often have multifocal tumours in the thyroid...
April 2017: Endocrine-related Cancer
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