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https://www.readbyqxmd.com/read/28212889/inhibition-of-proliferation-and-invasion-in-2d-and-3d-models-by-2-methoxyestradiol-in-human-melanoma-cells
#1
R R Massaro, F Faião-Flores, V W Rebecca, S Sandri, D K Alves-Fernandes, P C Pennacchi, K S M Smalley, S S Maria-Engler
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28212572/concurrent-gene-alterations-with-egfr-mutation-and-treatment-efficacy-of-egfr-tkis-in-chinese-patients-with-non-small-cell-lung-cancer
#2
Wentao Hu, Yahui Liu, Jian Chen
PURPOSE: We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. METHODS: Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#3
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28206962/pi3k-pathway-mutations-are-associated-with-longer-time-to-local-progression-after-radioembolization-of-colorectal-liver-metastases
#4
Etay Ziv, Michael Bergen, Hooman Yarmohammadi, F Ed Boas, E Nadia Petre, Constantinos T Sofocleous, Rona Yaeger, David B Solit, Stephen B Solomon, Joseph P Erinjeri
PURPOSE: To establish the relationship between common mutations in the MAPK and PI3K signaling pathways and local progression after radioembolization. MATERIALS AND METHODS: Retrospective review of a HIPAA-compliant institutional review-board approved database identified 40 patients with chemo-refractory colorectal liver metastases treated with radioembolization who underwent tumor genotyping for hotspot mutations in 6 key genes in the MAPK/PI3K pathways (KRAS, NRAS, BRAF, MEK1, PIK3CA, and AKT1)...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#5
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198367/usp9x-regulates-ets-1-ubiquitination-and-stability-to-control-nras-expression-and-tumorigenicity-in-melanoma
#6
Harish Potu, Luke F Peterson, Malathi Kandarpa, Anupama Pal, Hanshi Sun, Alison Durham, Paul W Harms, Peter C Hollenhorst, Ugur Eskiocak, Moshe Talpaz, Nicholas J Donato
ETS transcription factors are commonly deregulated in cancer by chromosomal translocation, overexpression or post-translational modification to induce gene expression programs essential in tumorigenicity. Targeted destruction of these proteins may have therapeutic impact. Here we report that Ets-1 destruction is regulated by the deubiquitinating enzyme, Usp9x, and has major impact on the tumorigenic program of metastatic melanoma. Ets-1 deubiquitination blocks its proteasomal destruction and enhances tumorigenicity, which could be reversed by Usp9x knockdown or inhibition...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28197208/molecular-mutations-and-their-cooccurrences-in-cytogenetically-normal-acute-myeloid-leukemia
#7
REVIEW
Mengning Wang, Chuanwei Yang, Le Zhang, Dale G Schaar
Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28193149/taqman-probes-as-blocking-agents-for-enriched-pcr-amplification-and-dna-melting-analysis-of-mutant-genes
#8
Irina V Botezatu, Irina O Panchuk, Anna M Stroganova, Anastasia I Senderovich, Valentina N Kondratova, Valery P Shelepov, Anatoly V Lichtenstein
Asymmetric PCR and DNA melting analysis with TaqMan probes applied for mutation detection is effectively used in clinical diagnostics. The method is simple, cost-effective, and carried out in a closed-tube format, minimizing time, labor, and risk of sample cross-contamination. Although DNA melting analysis is more sensitive than Sanger sequencing (mutation detection thresholds are ~5% and 15%-20%, respectively), it is less sensitive than more labor-intensive and expensive techniques such as pyrosequencing and droplet digital PCR...
February 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28191690/mutational-profiling-of-acral-melanomas-in-korean-populations
#9
Joon Ho Shim, Hyun-Tae Shin, Jiho Park, Ji-Hye Park, Jong-Hee Lee, Jun-Mo Yang, Duk-Hwan Kim, Kee-Taek Jang, Dong-Youn Lee
The proportion of acral melanoma (AM) is much higher in Asian populations than in Caucasians populations. Although mutational profiles associated with AM have been discovered in Caucasian populations, knowledge of its genetic alterations in the Asian populations is limited. To describe the molecular nature of AM in Korean patients, we performed mutational profilinge of AM and matched normal tissues of in patients. Fifty-one formalin-fixed paraffin-embedded AM samples and 32 matched pairs of from patients' saliva DNA were analyzed by next-generation sequencing...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28188776/aurora-a-overexpression-aurka-is-driven-by-foxm1-and-mapk-erk-activation-in-melanoma-cells-harbouring-braf-or-nras-mutations-impact-on-melanoma-prognosis-and-therapy
#10
Joan Anton Puig-Butille, Antònia Vinyals, Josep R Ferreres, Paula Aguilera, Eduard Cabré, Gemma Tell-Martí, Joaquim Marcoval, Francesca Mateo, Luís Palomero, Celia Badenas, Josep M Piulats, Josep Malvehy, Miquel A Pujana, Susana Puig, Àngels Fabra
The cell cycle-related genes AURORA A and Forkhead box M1 (FOXM1) are overexpressed in melanoma. We show here that AURKA overexpression is associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAF(V600E) mutation. AURKA overexpression may also be driven to increased promoter activation through elements such as ETS and FOXM1 found within the 5' proximal promoter region. Activated MAPK-ERK signalling pathway mediates robust AURKA promoter activation, thereby knockdown of BRAF(V600E) and ERK inhibition results in reduced AURKA transcription and expression...
February 7, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28188750/kras-and-pik3ca-mutations-in-colorectal-adenocarcinomas-correlate-with-aggressive-histological-features-and-behavior
#11
Sejin Jang, Mineui Hong, Mi Kyung Shin, Byung Chun Kim, Hyung-Sik Shin, Eunsil Yu, Seung-Mo Hong, Jihun Kim, Sung Min Chun, Tae-Im Kim, Kyung-Chan Choi, Young Woong Ko, Jeong Won Kim
Tumor budding (TB) in colorectal carcinoma (CRC) is related to epithelial-mesenchymal transition (EMT) and has been recently characterized as an indicator of poor prognosis along with lymphovascular tumor emboli (LVE), perineural invasion (PNI), and an infiltrative growth pattern. Mutations in the genes of the Ras-MAPK and PI3K pathways are associated with EMT and an aggressive CRC phenotype and have been used in patient stratification for anti-EGF receptor therapies; however, the impact of these mutations on CRC morphology and behavior remains unclear...
February 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28186096/spitz-nevi-and-spitzoid-melanomas-exome-sequencing-and-comparison-with-conventional-melanocytic-nevi-and-melanomas
#12
Rossitza Lazova, Natapol Pornputtapong, Ruth Halaban, Marcus Bosenberg, Yalai Bai, Hao Chai, Michael Krauthammer
We performed exome sequencing of 77 melanocytic specimens composed of Spitz nevi (n=29), Spitzoid melanomas (n=27), and benign melanocytic nevi (n=21), and compared the results with published melanoma sequencing data. Our study highlights the prominent similarity between Spitzoid and conventional melanomas with similar copy number changes and high and equal numbers of ultraviolet-induced coding mutations affecting similar driver genes. Mutations in MEN1, PRKAR1A, and DNMT3A in Spitzoid melanomas may indicate involvement of the protein kinase A pathway, or a role of DNA methylation in the disease...
February 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28184004/ets-proto-oncogene-1-transcriptionally-up-regulates-the-cholangiocyte-senescence-associated-protein-cyclin-dependent-kinase-inhibitor-2a
#13
Steven P O'Hara, Patrick L Splinter, Christy E Trussoni, Maria J Lorenzo Pisarello, Lorena Loarca, Noah S Splinter, Bryce F Schutte, Nicholas F LaRusso
Primary sclerosing cholangitis (PSC) is a chronic, fibro-inflammatory cholangiopathy (disease of the bile ducts) of unknown pathogenesis. We reported that cholangiocyte senescence features prominently in PSC and neuroblastoma RAS viral oncogene homolog (NRAS) is activated in PSC cholangiocytes. Additionally, persistent microbial insult (e.g., lipopolysaccharides [LPS]) induces Cyclin Dependent Kinase Inhibitor 2A (CDKN2A/p16INK4a) expression and senescence in cultured cholangiocytes in an NRAS-dependent manner...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28179590/whole-exome-sequencing-identified-mutational-profiles-of-high-grade-colon-adenomas
#14
Sung Hak Lee, Seung Hyun Jung, Tae-Min Kim, Je-Keun Rhee, Hyeon-Chun Park, Min Sung Kim, Sung Soo Kim, Chang Hyeok An, Sug Hyung Lee, Yeun-Jun Chung
Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them. Mutational profiling of high-grade colon adenoma (HGCA) that just precedes colon carcinoma might identify not only novel adenoma-specific genes but also critical genes for its progression to carcinoma. For this, we performed whole-exome sequencing (WES) of 12 HGCAs and identified 11 non-hypermutated and one hypermutated (POLE-mutated) cases...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#15
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28170370/development-of-a-gene-panel-for-next-generation-sequencing-of-clinically-relevant-mutations-in-cell-free-dna-from-cancer-patients
#16
Umberto Malapelle, Clara Mayo de-Las-Casas, Danilo Rocco, Monica Garzon, Pasquale Pisapia, Nuria Jordana-Ariza, Maria Russo, Roberta Sgariglia, Caterina De Luca, Francesco Pepe, Alejandro Martinez-Bueno, Daniela Morales-Espinosa, María González-Cao, Niki Karachaliou, Santiago Viteri Ramirez, Claudio Bellevicine, Miguel Angel Molina-Vila, Rafael Rosell, Giancarlo Troncone
BACKGROUND: When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS: Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma...
February 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28157215/identification-of-a-genetically-defined-ultra-high-risk-group-in-relapsed-pediatric-t-lymphoblastic-leukemia
#17
P Richter-Pechańska, J B Kunz, J Hof, M Zimmermann, T Rausch, O R Bandapalli, E Orlova, G Scapinello, J C Sagi, M Stanulla, M Schrappe, G Cario, R Kirschner-Schwabe, C Eckert, V Benes, J O Korbel, M U Muckenthaler, A E Kulozik
In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial diagnosis. As relapse-specific genetic events, we identified activating mutations in NT5C2 (P=0.0001, Fisher's exact test), inactivation of TP53 (P=0.0007, Fisher's exact test) and duplication of chr17:q11.2-24.3 (P=0...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28154916/-diagnostics-of-malignant-melanoma-of-the-skin-recommendations-of-the-current-s3-guidelines-on-histology-and-molecular-pathology
#18
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...
February 2, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28153952/qmc-pcrx-a-novel-method-for-rapid-mutation-detection
#19
Henry O Ebili, James Hassall, Abutaleb Asiri, Hersh Ham-Karim, Wakkas Fadhil, Ayodeji Johnson Agboola, Mohammad Ilyas
AIMS: We previously described the quick multiplex consensus PCR (QMC-PCR) as a method for rapid mutation screening in low-quality template. QMC-PCR has two-stages: a prediagnostic multiplex (PDM) reaction followed by a single specific diagnostic reaction with high-resolution melting (HRM) analysis. We aimed to develop QMC-PCRx in which second stage was multiplexed to allow testing of multiple targets. METHODS: The PDM reaction was retained without change. For the second stage, in silico design was used to identify targets amenable to a multiplex specific diagnostic reaction and multiplex HRM (mHRM) analysis...
February 2, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28152414/coexisting-and-cooperating-mutations-in-npm1-mutated-acute-myeloid-leukemia
#20
Jay L Patel, Jonathan A Schumacher, Kimberly Frizzell, Shelly Sorrells, Wei Shen, Adam Clayton, Rakhi Jattani, Todd W Kelley
NPM1 insertion mutations represent a common recurrent genetic abnormality in acute myeloid leukemia (AML) patients. The frequency of these mutations varies from approximately 30% overall up to 50% in patients with a normal karyotype. Several recent studies have exploited advances in massively parallel sequencing technology to shed light on the complex genomic landscape of AML. We hypothesize that variant allele fraction (VAF) data derived from massively parallel sequencing studies may provide further insights into the clonal architecture and pathogenesis of NPM1-driven leukemogenesis...
January 23, 2017: Leukemia Research
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