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https://www.readbyqxmd.com/read/29653267/emerging-landscape-of-circular-rnas-in-lung-cancer
#1
Wei Hu, Zhuo-Yue Bi, Zhen-Long Chen, Cong Liu, Lin-Lin Li, Feng Zhang, Qun Zhou, Wei Zhu, Yang-Yi-Yan Song, Bo-Tao Zhan, Qian Zhang, Yong-Yi Bi, Cheng-Cao Sun, De-Jia Li
Lung cancer, the leading cause of cancer deaths worldwide, is characterized with malignant cell growth. Advances in next-generation sequencing has helped us further understand RNA and identify novel circular RNAs (circRNAs) that may be useful in the early diagnosis and treatment of lung cancer. Similar to other noncoding RNAs, circRNAs present diverse biological functions in normal and disease states, including various types of cancers. This review focuses mainly on the poorly understood functions of circRNA in lung cancer...
April 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29650893/-towards-development-of-innovative-cancer-therapies-trans-omics-approach
#2
Reika Kawabata-Iwakawa, Masahiko Nishiyama
Comprehensive genomic and transcriptome analyses using next-generation sequencing(NGS)analysis has lead a discovery of a variety of novel driver gene mutations and new therapeutic targets for cancer patients, and has remarkably improved outcome of the patients through the development novel molecular targeting drugs. Even so, in so-called intractable or refractory cancers, those "druggable"alterations common to the diseases are rarely found due to the high diversity of the tumor. Furthermore, most of molecular target therapy is known to acquire the resistance to the drug by means of multiple factors such as up-regulation of the partially inhibited pathway, mutation of the target, activation of alternative pathways, histological translocation, and oncogene de-addiction...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29650684/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-for-central-nervous-system-metastases-from-non-small-cell-lung-cancer
#3
REVIEW
Manmeet S Ahluwalia, Kevin Becker, Benjamin P Levy
Central nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood-brain barrier (BBB), creating a major unmet need for the development of agents with good BBB-penetrating biopharmaceutical properties...
April 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29649618/preimplantation-high-resolution-hla-sequencing-using-next-generation-sequencing
#4
Maryam Rafati, Mohammad Mahdi Akhondi, Mohammad Reza Sadeghi, Seyedeh Zahra Tara, Saeed Reza Ghaffari
Hematopoietic Stem Cell Transplantation (HSCT) is the only therapeutic option in a number of heritable hematologic disorders as well as hematologic cancers. Many parents and families fail to find an HLA-identical donor for their affected family member. In such cases, conceiving for a savior baby remains the only option especially in countries without access to national registries. By means of Next Generation Sequencing (NGS) techniques, in a single experiment on single cell products of IVF, a healthy HLA-identical embryo can be implanted in the uterus of a concerned mother...
April 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29649374/precision-therapy-of-head-and-neck-squamous-cell-carcinoma
#5
P J Polverini, N J D'Silva, Y L Lei
Precision medicine is an approach to disease prevention and treatment that takes into account genetic variability and environmental and lifestyle influences that are unique to each patient. It facilitates stratification of patient populations that vary in their susceptibility to disease and response to therapy. Shared databases and the implementation of new technology systems designed to advance the integration of this information will enable health care providers to more accurately predict and customize prevention and treatment strategies for patients...
April 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29649263/validation-of-czecanca-czech-cancer-panel-for-clinical-application-for-targeted-ngs-based-analysis-of-hereditary-cancer-syndromes
#6
Jana Soukupova, Petra Zemankova, Klara Lhotova, Marketa Janatova, Marianna Borecka, Lenka Stolarova, Filip Lhota, Lenka Foretova, Eva Machackova, Viktor Stranecky, Spiros Tavandzis, Petra Kleiblova, Michal Vocka, Hana Hartmannova, Katerina Hodanova, Stanislav Kmoch, Zdenek Kleibl
BACKGROUND: Carriers of mutations in hereditary cancer predisposition genes represent a small but clinically important subgroup of oncology patients. The identification of causal germline mutations determines follow-up management, treatment options and genetic counselling in patients' families. Targeted next-generation sequencing-based analyses using cancer-specific panels in high-risk individuals have been rapidly adopted by diagnostic laboratories. While the use of diagnosis-specific panels is straightforward in typical cases, individuals with unusual phenotypes from families with overlapping criteria require multiple panel testing...
2018: PloS One
https://www.readbyqxmd.com/read/29648920/functional-domain-analysis-of-sox18-transcription-factor-using-a-single-chain-variable-fragment-based-approach
#7
Frank R Fontaine, Stephen Goodall, Jeremy W Prokop, Christopher B Howard, Mehdi Moustaqil, Somuah Kumble, Daniel T Rasicci, Geoffrey W Osborne, Yann Gambin, Emma Sierecki, Martina L Jones, Johannes Zuegg, Stephen Mahler, Mathias Francois
Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More recently, a new application for antibodies has emerged as crystallisation scaffolds for difficult to crystallise proteins, such as transcription factors. Only in a few rare cases, antibodies have been used to modulate the activity of transcription factors, and there is a real gap in our knowledge on how to efficiently design antibodies to interfere with transcription...
April 12, 2018: MAbs
https://www.readbyqxmd.com/read/29644010/value-based-genomics
#8
REVIEW
Jun Gong, Kathy Pan, Marwan Fakih, Sumanta Pal, Ravi Salgia
Advancements in next-generation sequencing have greatly enhanced the development of biomarker-driven cancer therapies. The affordability and availability of next-generation sequencers have allowed for the commercialization of next-generation sequencing platforms that have found widespread use for clinical-decision making and research purposes. Despite the greater availability of tumor molecular profiling by next-generation sequencing at our doorsteps, the achievement of value-based care, or improving patient outcomes while reducing overall costs or risks, in the era of precision oncology remains a looming challenge...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29642553/genomic-profiling-on-an-unselected-solid-tumor-population-reveals-a-highly-mutated-wnt-%C3%AE-catenin-pathway-associated-with-oncogenic-egfr-mutations
#9
Jingrui Jiang, Alexei Protopopov, Ruobai Sun, Stephen Lyle, Meaghan Russell
Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples...
April 9, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29630047/simple-and-rapid-method-to-obtain-high-quality-tumor-dna-from-clinical-pathological-specimens-using-touch-imprint-cytology
#10
Kenji Amemiya, Yosuke Hirotsu, Toshio Oyama, Masao Omata
It is critical to determine the mutational status in cancer before administration and treatment of specific molecular targeted drugs for cancer patients. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissues are widely used for genetic testing. However, FFPE DNA is generally damaged and fragmented during the fixation process with formalin. Therefore, FFPE DNA is sometimes not adequate for genetic testing because of low quality and quantity of DNA. Here we present a method of touch imprint cytology (TIC) to obtain genomic DNA from cancer cells, which can be observed under a microscope...
March 21, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29628467/targeted-therapy-according-to-next-generation-sequencing-based-panel-sequencing
#11
Motonobu Saito, Tomoyuki Momma, Koji Kono
Targeted therapy against actionable gene mutations shows a significantly higher response rate as well as longer survival compared to conventional chemotherapy, and has become a standard therapy for many cancers. Recent progress in next-generation sequencing (NGS) has enabled to identify huge number of genetic aberrations. Based on sequencing results, patients recommend to undergo targeted therapy or immunotherapy. In cases where there are no available approved drugs for the genetic mutations detected in the patients, it is recommended to be facilitate the registration for the clinical trials...
April 7, 2018: Fukushima Journal of Medical Science
https://www.readbyqxmd.com/read/29626621/first-in-human-phase-i-study-of-ac0010-a-mutant-selective-egfr-inhibitor-in-non-small-cell-lung-cancer-safety-efficacy-and-potential-mechanism-of-resistance
#12
Yuxiang Ma, Xin Zheng, Hongyun Zhao, Wenfeng Fang, Yang Zhang, Jieying Ge, Lu Wang, Weicong Wang, Ji Jiang, Shaokun Chuai, Zhou Zhang, Wanhong Xu, Xiao Xu, Pei Hu, Li Zhang
INTRODUCTION: AC0010 is a mutation-selective, third-generation EGFR tyrosine kinase inhibitor (TKI). This first-in-human phase I trial determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AC0010 in patients with advanced or recurrent NSCLC and acquired resistance to the first-generation EGFR-TKI. METHODS: Patients received escalating daily doses of AC0010 (50 to 600 mg) throughout 28-day cycles...
April 4, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29625863/circulating-cell-free-dna-for-non-invasive-cancer-management
#13
REVIEW
Caitlin M Stewart, Dana W Y Tsui
Cell-free DNA (cfDNA) was first identified in human plasma in 1948 and is thought to be released from cells throughout the body into the circulatory system. In cancer, a portion of the cfDNA originates from tumour cells, referred to as circulating-tumour DNA (ctDNA), and can contain mutations corresponding to the patient's tumour, for instance specific TP53 alleles. Profiling of cfDNA has recently become an area of increasing clinical relevance in oncology, in particular due to advances in the sensitivity of molecular biology techniques and development of next generation sequencing technologies, as this allows tumour mutations to be identified and tracked non-invasively...
March 11, 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29625247/added-value-of-50-gene-panel-sequencing-to-distinguish-multiple-primary-lung-cancers-from-pulmonary-metastases-a-systematic-investigation
#14
Paul Roepman, Alexandra Ten Heuvel, Karen C Scheidel, Tobias Sprong, Danielle A M Heideman, Cees A Seldenrijk, Gerarda J M Herder, J Alain Kummer
Differentiation between multiple primary lung cancers or pulmonary metastases has important implications for staging, prognosis, and treatment strategies. Clinical and immuno-histopathological criteria have been standardized; however, a substantial number of cases remain difficult to classify. Using next-generation sequencing it is now possible to improve classification of multiple lung cancer lesions. This study systematically investigated the value of routine morphological and immunohistochemical characteristics, p53 protein expression, TP53 mutation analysis, and 50-gene panel sequencing on 111 lesions from 50 patients with multiple lung lesions...
April 3, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29622700/hybrid-capture-based-tumor-sequencing-and-copy-number-analysis-to-confirm-origin-of-metachronous-metastases-in-brca1-mutant-cholangiocarcinoma-harboring-a-novel-ywhaz-braf-fusion
#15
Huat C Lim, Meagan Montesion, Thomas Botton, Eric A Collisson, Sarah E Umetsu, Spencer C Behr, John D Gordan, Phil J Stephens, Robin K Kelley
Biliary tract cancers such as cholangiocarcinoma represent a heterogeneous group of cancers that can be difficult to diagnose. Recent comprehensive genomic analyses in large cholangiocarcinoma cohorts have defined important molecular subgroups within cholangiocarcinoma that may relate to anatomic location and etiology [1-4] and may predict responsiveness to targeted therapies in development [5-7]. These emerging data highlight the potential for tumor genomics to inform diagnosis and treatment options in this challenging tumor type...
April 5, 2018: Oncologist
https://www.readbyqxmd.com/read/29621832/identifying-associations-between-somatic-mutations-and-clinicopathologic-findings-in-lung-cancer-pathology-reports
#16
Nishant Kumar, Laura J Tafe, John H Higgins, Jason D Peterson, Francise Blumental de Abreu, Sophie J Deharvengt, Gregory J Tsongalis, Christopher I Amos, Saeed Hassanpour
OBJECTIVE: We aim to build an informatics methodology capable of identifying statistically significant associations between the clinical findings of non-small cell lung cancer (NSCLC) recorded in patient pathology reports and the various clinically actionable genetic mutations identified from next-generation sequencing (NGS) of patient tumor samples. METHODS: We built an information extraction and analysis pipeline to identify the associations between clinical findings in the pathology reports of patients and corresponding genetic mutations...
February 2018: Methods of Information in Medicine
https://www.readbyqxmd.com/read/29621323/performance-comparison-of-three-dna-extraction-kits-on-human-whole-exome-data-from-formalin-fixed-paraffin-embedded-normal-and-tumor-samples
#17
Eric Bonnet, Marie-Laure Moutet, Céline Baulard, Delphine Bacq-Daian, Florian Sandron, Lilia Mesrob, Bertrand Fin, Marc Delépine, Marie-Ange Palomares, Claire Jubin, Hélène Blanché, Vincent Meyer, Anne Boland, Robert Olaso, Jean-François Deleuze
Next-generation sequencing (NGS) studies are becoming routinely used for the detection of novel and clinically actionable DNA variants at a pangenomic scale. Such analyses are now used in the clinical practice to enable precision medicine. Formalin-fixed paraffin-embedded (FFPE) tissues are still one of the most abundant source of cancer clinical specimen, unfortunately this method of preparation is known to degrade DNA and therefore compromise subsequent analysis. Some studies have reported that variant detection can be performed on FFPE samples sequenced with NGS techniques, but few or none have done an in-depth coverage analysis and compared the influence of different state-of-the-art FFPE DNA extraction kits on the quality of the variant calling...
2018: PloS One
https://www.readbyqxmd.com/read/29621252/xome-blender-a-novel-cancer-genome-simulator
#18
Roberto Semeraro, Valerio Orlandini, Alberto Magi
The adoption of next generation sequencing based methods in cancer research allowed for the investigation of the complex genetic structure of tumor samples. In the last few years, considerable importance was given to the research of somatic variants and several computational approaches were developed for this purpose. Despite continuous improvements to these programs, the validation of their results it's a hard challenge due to multiple sources of error. To overcome this drawback different simulation approaches are used to generate synthetic samples but they are often based on the addition of artificial mutations that mimic the complexity of genomic variations...
2018: PloS One
https://www.readbyqxmd.com/read/29620157/glucocorticoid-receptor-overexpression-slightly-shifts-microrna-expression-patterns-in-triple-negative-breast-cancer
#19
Dominik Buschmann, Ricardo González, Benedikt Kirchner, Claudia Mazzone, Michael W Pfaffl, Gustav Schelling, Ortrud Steinlein, Marlene Reithmair
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with limited options for clinical intervention. As with many solid tumors, TNBC is known to promote invasiveness and metastasis by secreting extracellular vesicles (EVs) capable of modulating the behaviour of recipient cells. Recent investigations have demonstrated that high expression levels of glucocorticoid receptor (GR) in TNBC are linked to therapy resistance, higher recurrence rates and increased mortality. In addition to activating protein-coding genes, GR is also involved in the expression of short non-coding RNAs including microRNAs (miRNAs or miRs)...
March 27, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29615460/clinical-and-pathological-characteristics-of-keap1-and-nfe2l2-mutated-non-small-cell-lung-carcinoma-nsclc
#20
Rieke Frank, Matthias Scheffler, Sabine Merkelbach-Bruse, Michaela Angelika Ihle, Anna Kron, Michael Rauer, Frank Ueckeroth, Katharina Koenig, Sebastian Michels, Rieke Fischer, Anna Eisert, Jana Fassunke, Carina Heydt, Monika Serke, Yon-Dschun Ko, Ulrich Gerigk, Thomas Geist, Britta Kaminsky, Lukas Heukamp, Mathieu Clement-Ziza, Reinhard Buettner, Juergen Wolf
BACKGROUND: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in many cancers and with squamous cell carcinoma formation in non-small cell lung cancer (NSCLC). However, few is known about frequency, histology-dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. PATIENTS AND METHODS: Tumor tissue of 1391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed...
April 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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