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https://www.readbyqxmd.com/read/29776954/role-of-elevated-phip-copy-number-as-a-prognostic-and-progression-marker-for-cutaneous-melanoma
#1
Vladimir Bezrookove, Mehdi Nosrati, James R Miller, David de Semir, Altaf A Dar, Elham Vosoughi, Edith Vaquero, Antje Sucker, Alexander J Lazar, Jeffrey E Gershenwald, Michael A Davies, Dirk Schadendorf, Mohammed Kashani-Sabet
PURPOSE: Previous studies have indicated an important role for pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis. Here we aimed to confirm the role of PHIP copy number in successive stages of melanoma progression. EXPERIMENTAL DESIGN: PHIP copy number was examined using fluorescence in situ hybridization (FISH) in three independent cohorts by recording the percentage of cells harboring > 3 copies of PHIP...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29775899/hispidulin-alleviates-high-glucose-induced-podocyte-injury-by-regulating-protective-autophagy
#2
Fengbo Wu, Sijia Li, Nan Zhang, Wei Huang, Xiang Li, Manyi Wang, Ding Bai, Bo Han
OBJECTIVES: Diabetic nephropathy (DN) is one of the most common complications in patients with diabetes, and the discovery of novel targeted therapeutic approaches for DN treatment still faces severe challenges. In the current study, we aimed to discover a novel natural product for potential DN treatment and determine its molecular mechanisms. MATERIALS AND METHODS: Methylthiazoltetrazolium (MTT) assay was employed to evaluate cell viability. Transmission electron microscopy, GFP-LC3 fluorescence fusion plasmid, and Annexin V/PI apoptosis assay were carried out to determine cellular autophagy and apoptosis...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29774112/rare-genetic-heterogeneity-within-single-tumor-discovered-for-the-first-time-in-colorectal-liver-metastases-after-liver-resection
#3
Mylène Sebagh, Nelly Bosselut, Alexandre Dos Santos, Marc-Antoine Allard, Aldrick Ruiz, Raphaël Saffroy, Daniel Cherqui, Eric Vibert, Denis Castaing, René Adam, Antonio Sa Cunha, Antoinette Lemoine
Effective individualized treatment of patients with colorectal liver metastases (CLM) requires tumor genotyping, usually based on the analysis of one single sample per patient. Therapy failure may partially be explained by sampling errors and/or intratumoral genetic heterogeneity. We aimed to demonstrate intratumoral genetic heterogeneity in CLM and enable pathologists to select tumor tissue for genotyping. All the tumors of 86 patients who underwent liver resection for a single CLM were reviewed. Of the 86 patients, 66 patients received chemotherapy and 20 patients did not receive chemotherapy before liver resection...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29767499/large-area-%C3%AE-cu2s-particles-stacked-nanorod-arrays-by-laser-ablation-in-liquid-and-their-strongly-structurally-enhanced-and-stable-visible-photoelectric-performances
#4
Haoming Bao, Hongwen Zhang, Le Zhou, Hao Fu, Guangqiang Liu, Yue Li, Weiping Cai
A flexible route is developed for fabrication of large area α-Cu2S nanorod arrays (NRAs) based on one step laser ablating a copper foil in CS2 liquid. It has been demonstrated that the obtained products are the high temperature phase α-Cu2S and consist of the nanorods vertically standing on the Cu foil, exhibiting the array. The nanorods were about 1 μm in length and around 100 nm in thickness, and built by stacking the nearly spherical and <110>-oriented nanoparticles (NPs) up. Such array can be peeled off from the foil and free-standing...
May 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29760015/novel-genomic-findings-in-multiple-myeloma-identified-through-routine-diagnostic-sequencing
#5
Georgina L Ryland, Kate Jones, Melody Chin, John Markham, Elle Aydogan, Yamuna Kankanige, Marisa Caruso, Jerick Guinto, Michael Dickinson, H Miles Prince, Kwee Yong, Piers Blombery
AIMS: Multiple myeloma is a genomically complex haematological malignancy with many genomic alterations recognised as important in diagnosis, prognosis and therapeutic decision making. Here, we provide a summary of genomic findings identified through routine diagnostic next-generation sequencing at our centre. METHODS: A cohort of 86 patients with multiple myeloma underwent diagnostic sequencing using a custom hybridisation-based panel targeting 104 genes. Sequence variants, genome-wide copy number changes and structural rearrangements were detected using an inhouse-developed bioinformatics pipeline...
May 14, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29755687/clinical-application-of-targeted-next-generation-sequencing-for-colorectal-cancer-patients-a-multicentric-belgian-experience
#6
Nicky D'Haene, Quitterie Fontanges, Nancy De Nève, Oriane Blanchard, Barbara Melendez, Monique Delos, Marie-Françoise Dehou, Calliope Maris, Nathalie Nagy, Emmanuel Rousseau, Josse Vandenhove, André Gilles, Carine De Prez, Laurine Verset, Marie-Paule Van Craynest, Pieter Demetter, Jean-Luc Van Laethem, Isabelle Salmon, Marie Le Mercier
International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755118/tumour-mutation-status-and-melanoma-recurrence-following-a-negative-sentinel-lymph-node-biopsy
#7
Nikki R Adler, Rory Wolfe, Grant A McArthur, John W Kelly, Andrew Haydon, Catriona A McLean, Victoria J Mar
BACKGROUND: A proportion of patients develop recurrence following a tumour-negative sentinel lymph node biopsy (SLNB). This study aimed to explore whether melanoma patients with BRAF or NRAS mutant tumours have an increased risk of developing disease recurrence following a negative SLNB compared to patients with wild-type tumours. METHODS: Prospective cohort study of melanoma patients at three tertiary referral centres in Melbourne, who underwent SLNB. Clinical, pathological and molecular characteristics and recurrence data were prospectively recorded...
May 14, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29753029/inherited-genetic-variants-associated-with-melanoma-braf-nras-subtypes
#8
Nancy E Thomas, Sharon N Edmiston, Irene Orlow, Peter A Kanetsky, Li Luo, David C Gibbs, Eloise A Parrish, Honglin Hao, Klaus J Busam, Bruce K Armstrong, Anne Kricker, Anne E Cust, Hoda Anton-Culver, Stephen B Gruber, Richard P Gallagher, Roberto Zanetti, Stefano Rosso, Lidia Sacchetto, Terence Dwyer, David W Ollila, Colin B Begg, Marianne Berwick, Kathleen Conway
BRAF and NRAS mutations arise early in melanoma development but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma (GEM) Study, 1223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms (SNPs) identified as low-penetrant melanoma risk variants. We used multinomial logistic regression to simultaneously examine each SNP's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features...
May 9, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29752895/adaptation-of-an-amplicon-based-human-cancer-next-generation-sequencing-panel-assay-for-murine-tumors
#9
David R Meier, Kristopher A Lofgren, Grzegorz T Gurda, Paraic A Kenny
Unlike humans, inbred genetically engineered mice have minimal inter-individual variation and, consequently, offer substantially increased statistical power for robust definition of recurrent cooperating cancer mutations. While technically feasible, whole exome sequencing is expensive and extremely data-intensive. Somatic mutation analysis using panels of 25-75 genes now provides detailed insight into the biology of human tumors. Here we report an adaptation for mouse tumors of a human PCR amplicon-based panel (Ion Torrent Cancer Hotspot Panel v2) allowing analysis of 18 cancer genes, including Kras, Nras, Hras, Pten, Pik3ca and Smad4, and encompassing regions homologous to more than 2000 known human cancer mutations...
May 9, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29752777/study-of-ras-mapk-pathway-gene-variants-in-chilean-patients-with-cryptorchidism
#10
F Rodríguez, C Vallejos, D Ponce, N Unanue, M I Hernández, S Célis, K Arcos, F Belmar, M T López, F Cassorla
Cryptorchidism is one of the most common congenital disorders in boys, and several genetic, hormonal, and environmental factors have been proposed as possible causes for this genitourinary defect. Genetic factors have been intensively searched, but relatively few pathogenic variants have been described. Cryptorchidism is a frequent finding in patients with RASopathies, a group of syndrome caused by mutations in genes of the Ras/MAPK pathway. Our aim was to determine whether patients with isolated cryptorchidism (IC) exhibit Ras/MAPK pathway gene variants associated with RASopathies...
May 11, 2018: Andrology
https://www.readbyqxmd.com/read/29745862/novel-functional-variants-at-the-gwas-implicated-loci-might-confer-risk-to-major-depressive-disorder-bipolar-affective-disorder-and-schizophrenia
#11
Leonid O Bryzgalov, Elena E Korbolina, Ilja I Brusentsov, Elena Y Leberfarb, Natalia P Bondar, Tatiana I Merkulova
BACKGROUND: A challenge of understanding the mechanisms underlying cognition including neurodevelopmental and neuropsychiatric disorders is mainly given by the potential severity of cognitive disorders for the quality of life and their prevalence. However, the field has been focused predominantly on protein coding variation until recently. Given the importance of tightly controlled gene expression for normal brain function, the goal of the study was to assess the functional variation including non-coding variation in human genome that is likely to play an important role in cognitive functions...
April 19, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29742286/study-of-promoter-hypomethylation-profiles-of-ras-oncogenes-in-hepatocellular-carcinoma-derived-from-hepatitis-c-virus-genotype-3a-in-pakistani-population
#12
Maria Maryam, Muhammad Idrees
Epigenetic modifications such as DNA methylation contribute to progression of Hepatitis C virus (HCV) infection to life-threatening hepatocellular carcinoma (HCC), by promoting the silencing of tumor suppressor genes due to DNA hypermethylation and by causing genomic instability due to global hypomethylation. However few studies addressed promoter region hypomethylation status of the oncogenes involved in HCV derived HCC. In this study, we analyzed the promoter region methylation pattern of RAS oncogenes (HRAS, KRAS, NRAS) using methylation-specific PCR (MSP) for 50 Chronic HCV patients infected with genotype 3a (27 HCC patients and 23 Control non-HCC patients)...
May 9, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29737864/panitumumab-in-the-treatment-of-metastatic-colorectal-cancer-including-wild-type-ras-kras-and-nras-mcrc
#13
Mark McGregor, Timothy J Price
The humanized monoclonal antibody panitumumab, targeted against EGFR, plays an important role in patients with metastatic colorectal cancer. This article reviews the body of evidence for panitumumab which demonstrates significant benefits across multiple lines of therapy in those without an extended RAS mutation. The use of panitumumab with RAS mutations is not beneficial and possibly harmful. Panitumumab is well tolerated with manageable toxicities. The role of panitumumab continues to evolve as understanding of sequencing of therapies grows...
May 8, 2018: Future Oncology
https://www.readbyqxmd.com/read/29736783/spindle-epithelial-tumor-with-thymus-like-differentiation-settle-a-next-generation-sequencing-study
#14
Todd M Stevens, Diana Morlote, Jeff Swensen, Michelle Ellis, Shuko Harada, Sharon Spencer, Carlos N Prieto-Granada, Andrew L Folpe, Zoran Gatalica
Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a malignant biphasic neoplasm of the thyroid or neck with propensity for late metastasis. Unlike synovial sarcoma, its main morphologic mimic, SETTLE lacks synovial sarcoma-associated translocations. A single case of SETTLE has shown a KRAS mutation but to date no comprehensive next generation sequencing studies of this rare neoplasm have been undertaken. Herein, we subjected 5 well defined cases of SETTLE to direct sequence analysis of 592 genes and fusion gene analysis of 52 genes frequently rearranged in human cancers...
May 7, 2018: Head and Neck Pathology
https://www.readbyqxmd.com/read/29736211/therapeutic-effects-of-targeting-ras-erk-signaling-in-giant-congenital-melanocytic-nevi
#15
Qingxiong Yu, Min Wu, Lingling Sheng, Qingfeng Li, Feng Xie
Most giant congenital melanocytic nevi (GCMN) exhibit an activating mutation in NRAS. Constitutive activation of the RAS-ERK signaling pathway induces proliferation in nevus cells and plays a pivotal role in melanoma development. In this study, we studied the efficacy of RAS-ERK pathway targeted therapy in GCMN. We isolated nevus cells from GCMN (GNCs) and compared the morphology of GNCs with normal melanocytes and the A375 melanoma cell line. Proliferation curves of GNCs and A375 cells were determined using Cell Counting Kit-8 assays...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29734047/efficacy-and-safety-of-single-agent-pan-human-epidermal-growth-factor-receptor-her-inhibitor-dacomitinib-in-locally-advanced-unresectable-or-metastatic-skin-squamous-cell-cancer
#16
S Cavalieri, F Perrone, R Miceli, P A Ascierto, L D Locati, C Bergamini, R Granata, S Alfieri, C Resteghini, D Galbiati, A Busico, N Paielli, R Patuzzo, A Maurichi, G Gallino, R Ruggeri, L Mariani, M Palla, L Licitra, P Bossi
BACKGROUND: In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial. METHODS: Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR)...
May 4, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29733873/runx1-promotes-cell-growth-in-human-t-cell-acute-lymphoblastic-leukemia-by-transcriptional-regulation-of-key-target-genes
#17
Catherine E Jenkins, Samuel Gusscott, Rachel J Wong, Olena O Shevchuk, Gurneet Rana, Vincenzo Giambra, Kateryna Tyshchenko, Rashedul Islam, Martin Hirst, Andrew P Weng
RUNX1 is frequently mutated in T-cell acute lymphoblastic leukemia (T-ALL). The spectrum of RUNX1 mutations has led to the notion that it acts as a tumor suppressor in this context; however, other studies have placed RUNX1 along with transcription factors TAL1 and NOTCH1 as core drivers of an oncogenic transcriptional program. To reconcile these divergent roles, we knocked down RUNX1 in human T-ALL cell lines and deleted Runx1 or Cbfb in primary mouse T-cell leukemias. RUNX1 depletion consistently resulted in reduced cell proliferation and increased apoptosis...
May 4, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29731264/comprehensive-expression-analysis-of-tnf-related-apoptosis-inducing-ligand-and-its-receptors-in-colorectal-cancer-correlation-with-mapk-alterations-and-clinicopathological-associations
#18
Spyridon Tsikalakis, Ilenia Chatziandreou, Nikolaos V Michalopoulos, Georgios E Theodoropoulos, Stratigoula Sakellariou, Penelope Korkolopoulou, Efstratios Patsouris, Angelica A Saetta
TNF-related, apoptosis-inducing ligand (TRAIL) apoptotic pathway constitutes a promising therapeutic target due to high selectivity and low toxicity of TRAIL targeting agents when administered in combination therapies. 106 colorectal cancers were examined for: relative mRNA expression of TRAIL pathway genes, decoy receptors TRAIL-R3 and TRAIL-R4 promoter methylation and the presence of KRAS, NRAS, BRAF mutations. Elevated mRNA levels were observed in 26%, 15%, 13%, 12% and 10% of the cases for TRAIL-R4, TRAIL-R3, TRAIL-R2, TRAIL-R1 and TRAIL genes respectively...
May 1, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29730071/predictive-factors-of-synchronous-colorectal-peritoneal-metastases-development-of-a-nomogram-and-study-of-its-utilities-using-decision-curve-analysis
#19
Shaobo Mo, Weixing Dai, Wenqiang Xiang, Qingguo Li, Renjie Wang, Guoxiang Cai
BACKGROUND: The objective of this study was to summarize the clinicopathological and molecular features of synchronous colorectal peritoneal metastases (CPM). We then combined clinical and pathological variables associated with synchronous CPM into a nomogram and confirmed its utilities using decision curve analysis. MATERIALS AND METHODS: Synchronous metastatic colorectal cancer (mCRC) patients who received primary tumor resection and underwent KRAS, NRAS, and BRAF gene mutation detection at our center from January 2014 to September 2015 were included in this retrospective study...
May 3, 2018: International Journal of Surgery
https://www.readbyqxmd.com/read/29726952/comprehensive-genetic-analysis-of-follicular-thyroid-carcinoma-predicts-prognosis-independent-of-histology
#20
Norman G Nicolson, Timothy D Murtha, Weilai Dong, Johan O Paulsson, Jungmin Choi, Andrea L Barbieri, Taylor C Brown, John W Kunstman, Catharina Larsson, Manju L Prasad, Reju Korah, Richard P Lifton, C Christofer Juhlin, Tobias Carling
Context: Follicular thyroid cancer (FTC) is classified into minimally invasive (miFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wiFTC) subtypes, according to the 2017 World Health Organization (WHO) guidelines. The genetic signatures of these subtypes may be crucial for diagnosis, prognosis, and treatment, but have not been described. Objective: Identify and describe the genetic underpinnings of subtypes of follicular thyroid cancer. Methods: Thirty-nine tumors, comprising 12 miFTCs, 17 eaFTCs, and 10 wiFTCs were whole-exome sequenced and analyzed...
May 2, 2018: Journal of Clinical Endocrinology and Metabolism
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