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https://www.readbyqxmd.com/read/28928972/screening-of-mutations-in-the-additional-sex-combs-like-1-transcriptional-regulator-tumor-protein-p53-and-kras-proto-oncogene-gtpase-nras-proto-oncogene-gtpase-genes-of-patients-with-myelodysplastic-syndrome
#1
Carolina Leite, Lucas Delmonico, Gilda Alves, Romario José Gomes, Mariana Rodrigues Martino, Aline Rodrigues da Silva, Aline Dos Santos Moreira, Maria Christina Maioli, Luciano Rios Scherrer, Elenice Ferreira Bastos, Roberto Irineu, Maria Helena Ornellas
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, different degrees of cellular dysplasia, and increased risk of progression to acute myeloid leukemia. International Prognostic Scoring System is the gold standard for MDS classification; however, patients exhibiting different clinical behaviors often coexist in the same group, indicating that the currently available scoring systems are insufficient. The genes that have recently been identified as mutated in MDS, including additional sex combs like 1, transcriptional regulator (ASXL1), tumor protein p53 (TP53), and KRAS proto-oncogene and GTPase (KRAS)/NRAS proto-oncogene, GTPase (NRAS), may contribute to a more comprehensive classification, as well as to the prognosis and progression of the disease...
October 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28926605/assessment-of-common-somatic-mutations-of-egfr-kras-braf-nras-in-pulmonary-non-small-cell-carcinoma-using-iplex%C3%A2-hs-a-new-highly-sensitive-assay-for-the-massarray%C3%A2-system
#2
Bobbie C Sutton, Ryan T Birse, Kevin Maggert, Tammy Ray, Jessica Hobbs, Amobi Ezenekwe, Jason Kazmierczak, Michael Mosko, Joan Kish, Andrew Bullock, Zonggao Shi, M Sharon Stack, Darryl Irwin
Increased early detection and personalized therapy for lung cancer have coincided with greater use of minimally invasive sampling techniques such as endobronchial ultrasound-guided biopsy (EBUS), endoscopic ultrasound-guided biopsy (EUS), and navigational biopsy, as well as thin needle core biopsies. As many lung cancer patients have late stage disease and other comorbidities that make open surgical procedures hazardous, the least invasive biopsy technique with the highest potential specimen yield is now the preferred first diagnostic study...
2017: PloS One
https://www.readbyqxmd.com/read/28923882/mutational-profiling-of-acute-myeloid-leukemia-with-normal-cytogenetics-in-brazilian-patients-the-value-of-next-generation-sequencing-for-genomic-classification
#3
Thiago Rodrigo de Noronha, Miguel Mitne-Neto, Maria de Lourdes Chauffaille
Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients' risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28921907/dual-mapk-pi3k-pathway-inhibition-with-trametinib-and-gsk2141795-does-not-yield-clinical-benefit-in-metastatic-nras-mutant-and-wild-type-melanoma
#4
Alain P Algazi, Rosaura Esteve-Puig, Adi Nosrati, Brian Hinds, Adele Hobbs-Muthukumar, Prachi Nandoskar, Susana Ortiz-Urda, Paul B Chapman, Adil Daud
Aberrant MAPK and PI3K pathway signaling may drive the malignant phenotype in NRAS mutant and BRAF(WT) NRAS(WT) metastatic melanoma. To target these pathways NRAS mutant and BRAF(WT) NRAS(WT) patients received oral trametinib at 1.5 mg daily and GSK2141795 at 50 mg daily in a 2-cohort Simon 2-stage design. Participants had adequate end organ function and no more than 2 prior treatment regimens. Imaging assessments were performed at 8-week intervals. 10 NRAS mutant and 10 BRAF(WT) NRAS(WT) patients were enrolled...
September 16, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28919996/mek-inhibition-and-immune-responses-in-advanced-melanoma
#5
REVIEW
Reinhard Dummer, Egle Ramelyte, Sabrina Schindler, Olaf Thürigen, Mitchell P Levesque, Peter Koelblinger
phase II and III clinical trials demonstrated modest anti- tumor activity of Binimetinib (MEK162) - a potent allosteric inhibitor of MEK1 and MEK2- in patients with advanced NRAS mutant melanoma. The analysis of the NEMO study in NRAS mutated melanoma, has shown that pre-treatment with immunotherapy improved the outcome of binimetinib therapy. We discuss this finding in the context of in vitro and in vivo effects of MEK inhibition on immuno-critical pathways and interactions.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28915622/genomic-analysis-integrated-whole-exome-sequencing-of-neuroblastomas-identifies-genetic-mutations-in-axon-guidance-pathway
#6
Yuanyuan Li, Miki Ohira, Yong Zhou, Teng Xiong, Wen Luo, Chao Yang, Xiangchun Li, Zhibo Gao, Rui Zhou, Yohko Nakamura, Takehiko Kamijo, Yasuhiko Kaneko, Takeshi Taketani, Junichi Ueyama, Tatsuro Tajiri, Hongyan Zhang, Jian Wang, Huanming Yang, Ye Yin, Akira Nakagawara
Neuroblastoma (NB) is a childhood solid malignant tumor originating from precursor cells of the peripheral nervous system. We have previously established a risk classification system based on DNA copy number profiles. To further explore the pathogenesis of NBs in distinct risk groups, we performed whole-exome sequencing analysis of 57 primary and 7 recurrent/metastatic tumors with unique chromosomal aberration profiles as categorized by our genomic sub-grouping system. Overall, a low frequency of somatic mutations was found...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914674/frequent-pd-l1-expression-in-malignant-melanomas-of-the-vulva
#7
Banafsheh Saleh, Jörg Kriegsmann, Stephan Falk, Sebastian Aulmann
Blockade of immune checkpoint pathways such as the programmed cell death protein 1 pathway (PD-1/PD-L1) is an emerging approach in the treatment of solid tumors. In malignant melanoma, the efficiacy of antibodies against PD-L1 has been shown to be associated with PD-L1 protein expression. To evaluate whether this approach may be of use in the rare cases of primary melanoma of the vulva, we have evaluated a series of 13 cases for PD-L1 expression as well as additional molecular alterations of KIT, NRAS, KRAS, and BRAF...
September 13, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28911069/clinical-utility-of-circulating-dna-analysis-for-rapid-detection-of-actionable-mutations-to-select-metastatic-colorectal-patients-for-anti-egfr-treatment
#8
A R Thierry, S El Messaoudi, C Mollevi, J L Raoul, R Guimbaud, D Pezet, P Artru, E Assenat, C Borg, M Mathonnet, C De La Fouchardière, O Bouché, C Gavoille, C Fiess, B Auzemery, R Meddeb, E Lopez-Crapez, C Sanchez, B Pastor, M Ychou
Background: While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods: Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients)...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28903574/whole-exome-sequencing-of-aberrant-plasma-cells-in-a-patient-with-multiple-myeloma-minimal-residual-disease
#9
M Zatopkova, J Filipová, T Jelínek, P Vojta, T Sevcikova, M Simicek, L Rihova, R Bezdekova, K Growkova, Z Kufová, J Smejkalová, M Hajdúch, L Pour, J Minárik, A Jungová, V Maisnar, F Kryukov, R Hájek
Multiple myeloma is a plasma cell dyscrasia. It is the second most common hematological malignancy which is characterized by proliferation of clonal plasma cells producing harmful monoclonal immunoglobulin. Despite treatment modalities greatly evolved during the last decade, small amount of aberrant residual cells reside in patients after therapy and can cause relapse of the disease. Characterization of the residual, resistant clones can help to reveal important therapeutic targets for application of effective and precious treatment...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903572/biomarkers-in-immunoglobulin-light-chain-amyloidosis
#10
Z Kufová, T Sevcikova, K Growkova, P Vojta, J Filipová, Z Adam, L Pour, M Penka, R Rysava, P Němec, L Brozova, P Vychytilova, A Jurczyszyn, S Grosicki, A Barchnicka, M Hajdúch, M Simicek, R Hájek
Immunoglobulin light chain amyloidosis (AL amyloidosis - ALA) is a monoclonal gammopathy characterized by presence of aberrant plasma cells producing amyloidogenic immunoglobulin light chains. This leads to formation of amyloid fibrils in various organs and tissues, mainly in heart and kidney, and causes their dysfunction. As amyloid depositing in target organs is irreversible, there is a big effort to identify biomarker that could help to distinguish ALA from other monoclonal gammopathies in the early stages of disease, when amyloid deposits are not fatal yet...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28900470/mutational-frequency-of-kras-nras-idh2-pik3ca-and-egfr-in-north-indian-gallbladder-cancer-patients
#11
Aarti Sharma, Ashok Kumar, Niraj Kumari, Narendra Krishnani, Neeraj Rastogi
BACKGROUND: Gallbladder cancer (GBC) has a peculiar geographical distinction, with a high prevalence seen in North India and Chile. There are various aetiopathogenetic mechanisms of GBC causation; one of them is a series of pathogenic mutations, which is responsible for the malignant transformation of gallbladder epithelium. Therefore, the present study aimed to find out cancer-specific hot spot mutations in five major cancer-related genes KRAS exon1 &2, NRAS exon1, IDH2 exon, PIK3CA exon 20, IDH2 exon 4 and EGFR exon 20 in North Indian GBC patients and their association with clinicopathological variables...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28899979/clinical-performance-evaluation-of-the-idylla-nras-braf-mutation-test-on-retrospectively-collected-formalin-fixed-paraffin-embedded-colorectal-cancer-tissue
#12
Louise Johnston, Michael Power, Philip Sloan, Anna Long, Angela Silmon, Ben Chaffey, Andrea Jane Lisgo, Liam Little, Ellen Vercauteren, Torben Steiniche, Tine Meyer, John Simpson
AIMS: Understanding the molecular mechanisms of underlying disease has led to a movement away from the one-drug-fits-all paradigm towards treatment tailored to the genetic profile of the patient. The Biocartis Idylla platform is a novel fully automated, real-time PCR-based in vitro diagnostic system. The Idylla NRAS-BRAF mutation test has been developed for the qualitative detection of mutations in NRAS and BRAF oncogenes, facilitating genetic profiling of patients with cancer. The aim of this study was to carry out a formal clinical performance evaluation...
September 12, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28881731/detection-of-braf-nras-kit-gnaq-gna11-and-map2k1-2-mutations-in-russian-melanoma-patients-using-lna-pcr-clamp-and-biochip-analysis
#13
Marina Emelyanova, Lilit Ghukasyan, Ivan Abramov, Oxana Ryabaya, Evgenia Stepanova, Anna Kudryavtseva, Asiya Sadritdinova, Cholpon Dzhumakova, Tatiana Belysheva, Sergey Surzhikov, Lyudmila Lyubchenko, Alexander Zasedatelev, Tatiana Nasedkina
Target inhibitors are used for melanoma treatment, and their effectiveness depends on the tumor genotype. We developed a diagnostic biochip for the detection of 39 clinically relevant somatic mutations in the BRAF, NRAS, KIT, GNAQ, GNA11, MAP2K1 and MAP2K2 genes. We used multiplex locked nucleic acid (LNA) PCR clamp for the preferable amplification of mutated over wild type DNA. The amplified fragments were labeled via the incorporation of fluorescently labeled dUTP during PCR and were hybridized with specific oligonucleotides immobilized on a biochip...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875289/-diagnostics-of-malignant-melanoma-of-the-skin-recommendations-of-the-current-s3-guidelines-on-histology-and-molecular-pathology
#14
C Rose
The updated S3 guidelines on malignant melanoma were established in August 2016. The principles of diagnostics and classification are based on the histopathological results from the primary tumor and if necessary the sentinel lymph nodes. The most important factor for prognosis is the tumor thickness according to Breslow and the detection of sentinel node micrometastases. The surgical safety margin after excision is dependent on the tumor thickness. Furthermore, ulceration of the primary tumor and presence of mitosis in melanomas less than 1 mm in thickness are also considered in the T‑classification...
September 5, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28873354/mutation-of-nras-is-a-rare-genetic-event-in-ovarian-low-grade-serous-carcinoma
#15
Deyin Xing, Yohan Suryo Rahmanto, Felix Zeppernick, Charlotte G Hannibal, Susanne K Kjaer, Russell Vang, Ie-Ming Shih, Tian-Li Wang
Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of serous borderline tumor (SBT) to invasive low grade serous carcinoma (LGSC) remains largely unknown. While mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression...
September 2, 2017: Human Pathology
https://www.readbyqxmd.com/read/28866095/differential-expression-of-muc4-gpr110-and-il2ra-defines-two-groups-of-crlf2-rearranged-acute-lymphoblastic-leukemia-patients-with-distinct-secondary-lesions
#16
Teresa Sadras, Susan L Heatley, Chung H Kok, Phuong Dang, Kate M Galbraith, Barbara J McClure, Walter Muskovic, Nicola C Venn, Sarah Moore, Michael Osborn, Tamas Revesz, Andrew S Moore, Timothy P Hughes, David Yeung, Rosemary Sutton, Deborah L White
CRLF2-rearrangements (CRLF2-r) occur frequently in Ph-like B-ALL, a high-risk ALL sub-type characterized by a signaling profile similar to Ph + ALL, however accumulating evidence indicates genetic heterogeneity within CRLF2-r ALL. We performed thorough genomic characterization of 35 CRLF2-r cases (P2RY8-CRLF2 n = 18; IGH-CRLF2 n = 17). Activating JAK2 mutations were present in 34% of patients, and a CRLF2-F232C mutation was identified in an additional 17%. IKZF1 deletions were detected in 63% of cases...
September 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28863071/an-ovarian-adenocarcinoma-with-combined-low-grade-serous-and-mesonephric-morphologies-suggests-a-m%C3%A3-llerian-origin-for-some-mesonephric-carcinomas
#17
David B Chapel, Nancy M Joseph, Thomas Krausz, Ricardo R Lastra
Mesonephric carcinomas are rare adenocarcinomas of the female genital tract that occur most commonly in the uterine cervix. They are classically thought to arise from benign mesonephric remnants, and are rarely reported at other sites in the gynecologic tract. Here we present an interesting biphenotypic ovarian adenocarcinoma with intimately associated but distinct components of both low-grade serous carcinoma and mesonephric-like carcinoma. A serous borderline tumor was present adjacent to the invasive carcinoma, and no benign mesonephric precursors were identified...
August 31, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28860801/nras-mutant-melanoma-current-challenges-and-future-prospect
#18
REVIEW
Eva Muñoz-Couselo, Ester Zamora Adelantado, Carolina Ortiz, Jesús Soberino García, José Perez-Garcia
Melanoma is one of the most common cutaneous cancers worldwide. Activating mutations in RAS oncogenes are found in a third of all human cancers and NRAS mutations are found in 15%-20% of melanomas. The NRAS-mutant subset of melanoma is more aggressive and associated with poorer outcomes, compared to non-NRAS-mutant melanoma. Although immune checkpoint inhibitors and targeted therapies for BRAF-mutant melanoma are transforming the treatment of metastatic melanoma, the ideal treatment for NRAS-mutant melanoma remains unknown...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28859058/preoperative-chemoradiation-with-capecitabine-irinotecan-and-cetuximab-in-rectal-cancer-significance-of-pre-treatment-and-post-resection-ras-mutations
#19
Simon Gollins, Nick West, David Sebag-Montefiore, Arthur Sun Myint, Mark Saunders, Shabbir Susnerwala, Phil Quirke, Sharadah Essapen, Leslie Samuel, Bruce Sizer, Jane Worlding, Katie Southward, Gemma Hemmings, Emma Tinkler-Hundal, Morag Taylor, Daniel Bottomley, Philip Chambers, Emma Lawrie, Andre Lopes, Sandy Beare
BACKGROUND: The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. METHODS: In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin...
August 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28853218/mutational-status-of-nras-kras-and-ptpn11-genes-is-associated-with-genetic-cytogenetic-features-in-children-with-b-precursor-acute-lymphoblastic-leukemia
#20
Der-Cherng Liang, Shih-Hsiang Chen, Hsi-Che Liu, Chao-Ping Yang, Ting-Chi Yeh, Tang-Her Jaing, Iou-Jih Hung, Jen-Yin Hou, Tung-Huei Lin, Chun-Hui Lin, Lee-Yung Shih
BACKGROUND: We aimed to investigate the frequencies and the association with genetic/cytogenetic abnormalities as well as prognostic relevance of RAS pathway mutations in Taiwanese children with B-precursor acute lymphoblastic leukemia (ALL), the largest cohort in Asians. PROCEDURE: Between 1995 and 2012, marrow samples at diagnosis from 535 children were studied for NRAS, KRAS, and PTPN11 mutations. The mutational status of each gene was correlated with the clinico-hematological features, recurrent genetic abnormalities, and outcomes for those treated with TPOG-ALL-2002 protocol (n = 346)...
August 29, 2017: Pediatric Blood & Cancer
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