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https://www.readbyqxmd.com/read/28433252/nrasq61r-immunohistochemistry-detects-both-nrasq61r-and-krasq61r-mutations-in-colorectal-cancer
#1
Jie-Yang Jhuang, Chang-Tsu Yuan, Yu-Lin Lin, Mei-Ling Cheng, Jau-Yu Liau, Jia-Huei Tsai
The NRASQ61R monoclonal antibody (clone sp174) is a mutation-specific antibody that is increasingly being used to detect the NRAS(Q61R) mutation in melanomas. This antibody has been reported to be highly correlated with the NRAS(Q61R) mutation status in melanomas and follicular neoplasms of the thyroid gland. However, its utility in colorectal carcinoma (CRC) has remained largely unknown. In this study, we assessed the sensitivity, specificity, and diagnostic utility of NRASQ61R immunohistochemistry in a cohort consisting of tissue sections of 113 CRCs, which were molecularly profiled for the KRAS, NRAS, and BRAF mutations...
April 19, 2017: Pathology
https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#2
Pedro da Silva-Coelho, Leonie I Kroeze, Kenichi Yoshida, Theresia N Koorenhof-Scheele, Ruth Knops, Louis T van de Locht, Aniek O de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M A Blijlevens, Petra Muus, Gerwin Huls, Bert A van der Reijden, Seishi Ogawa, Joop H Jansen
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428551/enhanced-visible-light-photocatalytic-performance-of-cds-sensitized-tio2-nanorod-arrays-decorated-with-au-nanoparticles-as-electron-sinks
#3
Xin Gao, Xiangxuan Liu, Zuoming Zhu, Ying Gao, Qingbo Wang, Fei Zhu, Zheng Xie
In this paper, we propose a nanostructure with Au nanoparticles (NPs), as electron sinks, located at the most outside layer of CdS sensitized TiO2 nanorod arrays (TiO2 NRAs/CdS/Au). By the introduction of Au NPs, TiO2 NRAs/CdS/Au performs higher visible light photocatalytic capacity in the degradation of unsymmetrical dimethylhydrazine wastewater than TiO2 NRAs/CdS. The optimal deposition time for Au NPs is 30 s. The visible light induced degradation ability of TiO2 NRAs/CdS/Au (30 s) is 1.4 times that of TiO2 NRAs/CdS...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427158/the-varied-distribution-and-impact-of-ras-codon-and-other-key-dna-alterations-across-the-translocation-cyclin-d-subgroups-in-multiple-myeloma
#4
Caleb K Stein, Charlotte Pawlyn, Shweta Chavan, Leo Rasche, Niels Weinhold, Adam Corken, Amy Buros, Pieter Sonneveld, Graham H Jackson, Ola Landgren, Tariq Mughal, Jie He, Bart Barlogie, P Leif Bergsagel, Faith E Davies, Brian A Walker, Gareth J Morgan
We examined a set of 805 cases that underwent DNA sequencing using the FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling. Known and likely variant calls from the mutational data were analyzed for significant associations with gene expression defined translocation cyclin D (TC) molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424161/response-and-progression-on-midostaurin-in-advanced-systemic-mastocytosis-kit-d816v-and-other-molecular-markers
#5
Mohamad Jawhar, Juliana Schwaab, Nicole Naumann, Hans-Peter Horny, Karl Sotlar, Torsten Haferlach, Georgia Metzgeroth, Alice Fabarius, Peter Valent, Wolf-Karsten Hofmann, Nicholas C P Cross, Manja Meggendorfer, Andreas Reiter
In advanced systemic mastocytosis (advSM), disease evolution is often triggered by activating KIT mutations (D816V in >80% of cases) and by additional mutations, e.g. in SRSF2, ASXL1 and/or RUNX1 (S/A/R(pos), >60% of cases). In a recently reported phase-II-study, midostaurin, a multikinase/KIT inhibitor, demonstrated an overall response rate (ORR) of 60% in advSM but biomarkers predictive of response are lacking. We evaluated the impact of molecular markers (KIT D816V, S/A/R(pos)) at baseline and during follow-up in 38 midostaurin-treated advSM patients...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28416767/the-molecular-heterogeneity-of-sporadic-colorectal-cancer-with-different-tumor-sites-in-chinese-patients
#6
Junjie Peng, Dan Huang, Graeme Poston, Xiaoji Ma, Renjie Wang, Weiqi Sheng, Xiaoyan Zhou, Xiaoli Zhu, Sanjun Cai
PURPOSE: To assess the biological variability of clinical meaningful molecular markers and their clinical correlations in Chinese patients with colorectal cancer (CRC). MATERIALS AND METHODS: In this prospective observational study, frequencies and clinico-pathological features of RAS and BRAFV600E mutations, deficiency of DNA mismatch repair (dMMR) were evaluated in patients with colorectal cancer staged I-IV. The molecular heterogeneity between right-sided and left-sided colorectal cancers was studied in our series by classifying patients with different mutations and dMMR status...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410286/successful-treatment-with-imatinib-after-nilotinib-and-ipilimumab-in-a-c-kit-mutated-advanced-melanoma-patient-a-case-report
#7
Carla Murer, Pascale Kränzlin-Stieger, Lars E French, Reinhard Dummer, Simone M Goldinger
Treatment of melanoma remains a challenge in advanced disease. Recently, the molecular differentiation in BRAF-mutated, NRAS-mutated and c-kit-mutated melanomas led to new treatment strategies. Different trials show that imatinib or nilotinib lead to meaningful responses in c-kit-mutated melanoma patients. There are little published data on sequential inhibition using these two drugs in melanoma. We describe the sequential use of imatinib after nilotinib in a c-kit-mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine, nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor imatinib...
April 13, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28409271/unique-presentation-of-cutis-laxa-with-leigh-like-syndrome-due-to-echs1-deficiency
#8
S Balasubramaniam, L G Riley, D Bratkovic, D Ketteridge, N Manton, M J Cowley, V Gayevskiy, T Roscioli, M Mohamed, T Gardeitchik, E Morava, J Christodoulou
Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade...
April 13, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28408464/targetable-kinase-gene-fusions-in-high-risk-b-all-a-study-from-the-children-s-oncology-group
#9
Shalini C Reshmi, Richard C Harvey, Kathryn G Roberts, Eileen Stonerock, Amy Smith, Heather Jenkins, I-Ming Chen, Marc Valentine, Yu Liu, Yongjin Li, Ying Shao, John Easton, Debbie Payne-Turner, Zhaohui Gu, Thai Hoa Tran, Jonathan V Nguyen, Meenakshi Devidas, Yunfeng Dai, Nyla A Heerema, Andrew J Carroll, Elizabeth A Raetz, Michael J Borowitz, Brent L Wood, Anne L Angiolillo, Michael J Burke, Wanda L Salzer, Patrick A Zweidler-McKay, Karen R Rabin, William L Carroll, Jinghui Zhang, Mignon L Loh, Charles G Mullighan, Cheryl L Willman, Julie M Gastier-Foster, Stephen P Hunger
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed childhood B-ALL patients with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of which were excluded from additional analysis because of the presence of BCR-ABL1 (n=46) or ETV6-RUNX1 (n=11)...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28399112/cetuximab-in-treatment-of-metastatic-colorectal-cancer-final-survival-analyses-and-extended-ras-data-from-the-nordic-vii-study
#10
Tormod Kyrre Guren, Maria Thomsen, Elin H Kure, Halfdan Sorbye, Bengt Glimelius, Per Pfeiffer, Pia Österlund, Fridbjörn Sigurdsson, Inger Marie Bowitz Lothe, Astrid Marie Dalsgaard, Eva Skovlund, Thoralf Christoffersen, Kjell Magne Tveit
BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis. METHODS: A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28389780/computed-determination-of-the-in-vitro-optimal-chemocombinations-of-sphaeropsidin-a-with-chemotherapeutic-agents-to-combat-melanomas
#11
Aude Ingels, Carina Dinhof, Abhishek D Garg, Lucia Maddau, Marco Masi, Antonio Evidente, Walter Berger, Bieke Dejaegher, Véronique Mathieu
PURPOSE: Evasion to new treatments of advanced melanoma is still associated with a poor prognosis. Choosing the best combination of agents that can bypass resistance mechanisms remains a challenge. Sphaeropsidin A (Sph A) is a fungal bioactive secondary metabolite previously shown to force melanoma cells to undergo apoptosis via cell volume dysregulation. This work studied its in vitro combination with cytotoxic chemotherapeutics in a rational manner. METHODS: Four melanoma cell lines harboring different sensitivity levels to pro-apoptotic stimuli were used to build a predictive response surface model allowing the determination of the optimal in vitro combinations of Sph A with two drugs, i...
April 7, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28385781/monitoring-of-multiple-myeloma-by-quantification-of-recurrent-mutations-in-serum
#12
Even Holth Rustad, Eivind Coward, Emilie R Skytøen, Kristine Misund, Toril Holien, Therese Standal, Magne Børset, Vidar Beisvag, Ola Myklebost, Leonardo A Meza-Zepeda, Hong Yan Dai, Anders Sundan, Anders Waage
Circulating tumor DNA (ctDNA) is a promising biomarker to monitor tumor load and genome alterations. We have explored the presence of ctDNA in multiple myeloma patients and its relation to disease activity during long-term follow-up. We used digital droplet PCR to monitor recurrent mutations, mainly in mitogen activated protein kinase pathway genes NRAS, KRAS and BRAF. Mutations were identified by next generation sequencing or PCR of bone marrow plasma cells, and their presence analyzed in 251 archived serum samples obtained from 20 patients during up to 7 years...
April 6, 2017: Haematologica
https://www.readbyqxmd.com/read/28380455/targeted-next-generation-sequencing-of-mucosal-melanomas-identifies-frequent-nf1-and-ras-mutations
#13
Ioana Cosgarea, Selma Ugurel, Antje Sucker, Elisabeth Livingstone, Lisa Zimmer, Mirjana Ziemer, Jochen Utikal, Peter Mohr, Christiane Pfeiffer, Claudia Pföhler, Uwe Hillen, Susanne Horn, Dirk Schadendorf, Klaus G Griewank, Alexander Roesch
PURPOSE: Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown. EXPERIMENTAL DESIGN AND RESULTS: In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma...
March 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28380360/the-mutational-landscape-of-circulating-tumor-cells-in-multiple-myeloma
#14
Yuji Mishima, Bruno Paiva, Jiantao Shi, Jihye Park, Salomon Manier, Satoshi Takagi, Mira Massoud, Adriana Perilla-Glen, Yosra Aljawai, Daisy Huynh, Aldo M Roccaro, Antonio Sacco, Marzia Capelletti, Alexandre Detappe, Diego Alignani, Kenneth C Anderson, Nikhil C Munshi, Felipe Prosper, Jens G Lohr, Gavin Ha, Samuel S Freeman, Eliezer M Van Allen, Viktor A Adalsteinsson, Franziska Michor, Jesus F San Miguel, Irene M Ghobrial
The development of sensitive and non-invasive "liquid biopsies" presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28378855/genetic-and-epigenetic-alterations-of-tert-are-associated-with-inferior-outcome-in-adolescent-and-young-adult-patients-with-melanoma
#15
Brittani Seynnaeve, Seungjae Lee, Sumit Borah, Yongseok Park, Alberto Pappo, John M Kirkwood, Armita Bahrami
Progression of melanoma to distant sites in adolescents and young adults (AYAs) is not reliably predicted by clinicopathologic criteria. TERT promoter mutations when combined with BRAF/NRAS mutations correlate with adverse outcome in adult melanoma. To determine the prognostic value of TERT alterations in AYA melanoma, we investigated the association of TERT promoter mutations, as well as promoter methylation, an epigenetic alteration also linked to TERT upregulation, with TERT mRNA expression and outcome using a well-characterized cohort of 27 patients with melanoma (ages 8-25, mean 20)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28378457/dna-methylation-epigenotype-and-clinical-features-of-nras-mutation-colorectal-cancer
#16
Kiyoko Takane, Kiwamu Akagi, Masaki Fukuyo, Koichi Yagi, Tadatoshi Takayama, Atsushi Kaneda
Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome-wide DNA methylation analysis to classify CRC into distinct subgroups: high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)-high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP-low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers...
April 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28373299/integrated-genomic-analyses-reveal-frequent-tert-aberrations-in-acral-melanoma
#17
Winnie S Liang, William Hendricks, Jeffrey Kiefer, Jessica Schmidt, Shobana Sekar, John Carpten, David W Craig, Jonathan Adkins, Lori Cuyugan, Zarko Manojlovic, Rebecca F Halperin, Adrienne Helland, Sara Nasser, Christophe Legendre, Laurence H Hurley, Karthigayini Sivaprakasam, Douglas B Johnson, Holly Crandall, Klaus J Busam, Victoria Zismann, Valerie Deluca, Jeeyun Lee, Aleksandar Sekulic, Charlotte E Ariyan, Jeffrey Sosman, Jeffrey Trent
Genomic analyses of cutaneous melanoma (CM) have yielded biological and therapeutic insights, but understanding of non-ultraviolet (UV)-derived CMs remains limited. Deeper analysis of acral lentiginous melanoma (ALM), a rare sun-shielded melanoma subtype associated with worse survival than CM, is needed to delineate non-UV oncogenic mechanisms. We thus performed comprehensive genomic and transcriptomic analysis of 34 ALM patients. Unlike CM, somatic alterations were dominated by structural variation and absence of UV-derived mutation signatures...
April 2017: Genome Research
https://www.readbyqxmd.com/read/28371605/microrna-294-promotes-cellular-proliferation-and-motility-through-the-pi3k-akt-and-jak-stat-pathways-by-upregulation-of-nras-in-bladder-cancer
#18
Yongwei Li, Zhengfei Shan, Chu Liu, Diandong Yang, Jitao Wu, Changping Men, Yankai Xu
In our study we examined the role of microRNA-294 (miR-294) in bladder cancer and related mechanisms. Real-time polymerase chain reaction (RT-PCR) was performed to determine the expression level of miR-294. Western blot was used to determine the expression of NRAS, mainly factors in the PI3K/AKT and JAK/STAT pathways. Cell counting kit-8 assay, clonogenic assay, wound-healing assay, transwell and flow cytometry were used to explore, respectively, cell proliferation, survival, migration, invasion, and apoptosis of bladder cancer cell line T24...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28362711/ectopic-thyroid-tissue-immunohistochemistry-and-molecular-analysis
#19
Diana M Lin, Sara Javidiparsijani, Alexandra Vardouniotis, Lela Buckingham, Swathi B Reddy, Paolo Gattuso
Ectopic thyroid tissue is rare and controversial. Some experts consider it to always be metastatic thyroid carcinoma, whereas others consider it benign as long as it is restricted to few follicles without cytoarchitectural features of papillary thyroid carcinoma. Immunohistochemistry (IHC) and molecular studies have not yet been performed to further characterize this entity. We retrospectively searched our pathology files for all ectopic thyroid inclusions and reviewed clinicopathologic characteristics and concurrent thyroid pathologic findings...
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28356599/towards-personalized-medicine-in-melanoma-implementation-of-a-clinical-next-generation-sequencing-panel
#20
Blanca de Unamuno Bustos, Rosa Murria Estal, Gema Pérez Simó, Inmaculada de Juan Jimenez, Begoña Escutia Muñoz, Mercedes Rodríguez Serna, Victor Alegre de Miquel, Margarita Llavador Ros, Rosa Ballester Sánchez, Eduardo Nagore Enguídanos, Sarai Palanca Suela, Rafael Botella Estrada
Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples...
March 29, 2017: Scientific Reports
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