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https://www.readbyqxmd.com/read/28736627/personalized-and-precision-medicine-integrating-genomics-into-treatment-decisions-in-gastrointestinal-malignancies
#1
REVIEW
Trang H Au, Kai Wang, David Stenehjem, Ignacio Garrido-Laguna
The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC)...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28730258/morphology-with-immunohistochemical-and-genetic-profiling-of-high-grade-neuroendocrine-carcinoma-of-colon-a-case-report-with-review-of-literature
#2
Andrzej Wincewicz, Artur Kowalik, Sebastian Zięba, Stanisław Sułkowski, Stanisław Góźdź
Here we present a challenging case of a hepatic flexure colon tumor of 61-year-old woman with no primary lesion of lung cancer. Immunohistochemistry was applied and 50 genes were analyzed by next-generation sequencing (NGS) technology. The tumor contained medium to large size neoplastic cells with evident nucleoli to be diagnosed poorly differentiated neuroendocrine predominantly large cell carcinoma of colon [G3: World Health Organization (WHO) 2010] (pT3 N0: 7th edition pTNM). Cytokeratin (CK) AE1÷AE3 staining was predominantly membranous with partial distribution in "dot-like" pattern in perinecrotic cancer fields to be reminiscent of small cell carcinoma...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28730229/molecular-analysis-of-brca1-and-brca2-genes-by-next-generation-sequencing-and-ultrastructural-aspects-of-breast-tumor-tissue
#3
Corina Elena Mihalcea, Ana Maria Moroşanu, Daniela Murăraşu, Liliana Puiu, Sabin Aurel Cinca, Silviu Cristian Voinea, Nicolae Mirancea
In this paper, we focus our interest on the dynamics alterations of the tumor-stroma interface at the ultrastructural level and to detect BRCA1 and BRCA2 mutations using next generation sequencing (NGS) of breast tumor tissue. Electron microscopic investigation revealed some peculiar infrastructural alterations of the tumor cells per se as well as of the tumor-stroma interface: invadopodia, shedding microvesicles, altered morphology and reduced number of telocytes, different abnormalities of the microvasculature...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28727266/next-generation-sequencing-of-cytologic-preparations-an-analysis-of-quality-metrics
#4
David H Hwang, Elizabeth P Garcia, Matthew D Ducar, Edmund S Cibas, Lynette M Sholl
BACKGROUND: Next-generation sequencing (NGS) fails for many small biopsies (BXs) because of a low overall DNA concentration or tumor percentage. Cytology smears and liquid-based preparations (LBPs), or smears/LBPs, often contain abundant tumor cells and may provide adequate material for molecular testing when other materials are insufficient. This study examined the performance of smears/LBPs on a clinical NGS assay. METHODS: This study retrospectively reviewed quality metrics from consecutive smear/LBP, core BX, and cell block (CB) cases run on a hybrid-capture NGS assay interrogating 309 cancer-related genes...
July 20, 2017: Cancer
https://www.readbyqxmd.com/read/28723342/molecular-analysis-of-circulating-free-dna-from-lung-cancer-patients-in-routine-laboratory-practice-a-cross-platform-comparison-of-three-different-molecular-methods-for-mutation-detection
#5
Stephan Bartels, Sascha Persing, Britta Hasemeier, Elisa Schipper, Hans Kreipe, Ulrich Lehmann
Cell-free DNA (cfDNA), which is isolated from blood plasma, represents a noninvasive source for the detection of mutations conferring resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small-cell lung cancer patients. In advanced disease stages, performing regular biopsies is often not possible because of the general health condition of the patients. Furthermore, a biopsy of a single tumor lesion or metastasis may not reflect the heterogeneous genotype of the tumor and its metastases...
July 16, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#6
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28721068/patients-harboring-alk-rearrangement-adenocarcinoma-after-acquired-resistance-to-crizotinib-and-transformation-to-small-cell-lung-cancer-a-case-report
#7
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Li-Hua Zhong, Kai-Qi Du, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28717669/pitfalls-in-genetic-testing-a-case-of-a-snp-in-primer-annealing-region-leading-to-allele-dropout-in-brca1
#8
Felipe Carneiro Silva, Giovana Tardin Torrezan, Rafael Canfield Brianese, Raquel Stabellini, Dirce Maria Carraro
BACKGROUND: Hereditary breast and ovarian cancer is characterized by mutations in BRCA1 or BRCA2 genes and PCR-based screening techniques, such as capillary sequencing and next-generation sequencing (NGS), are considered gold standard methods for detection of pathogenic mutations in these genes. Single-nucleotide polymorphisms (SNPs) constitute a vast source of variation in the human genome and represent a risk for misdiagnosis in genetic testing, since the presence of a SNP in primer-annealing sites may cause false negative results due to allele dropout...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28717660/a-novel-molecular-diagnostics-platform-for-somatic-and-germline-precision-oncology
#9
Rubén Cabanillas, Marta Diñeiro, David Castillo, Patricia C Pruneda, Cristina Penas, Guadalupe A Cifuentes, Álvaro de Vicente, Noelia S Durán, Rebeca Álvarez, Gonzalo R Ordóñez, Juan Cadiñanos
BACKGROUND: Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28712319/primary-liver-cancer-genome-sequencing-translational-implications-and-challenges
#10
Demosthenes E Ziogas, Ioannis D Kyrochristos, Georgios K Glantzounis, Dimitrios Christodoulou, Evangelos Felekouras, Dimitrios H Roukos
The prognosis of primary liver cancer (PLC) remains poor and is explained by the slow progress in understanding the molecular pathways driving tumorigenesis, therapeutic resistance and relapse. For early PLCs, complete surgical resection is the only effective treatment, with sorafenib and, more recently, regorafenib prolonging overall survival by a few months. Areas covered: Application of next-generation sequencing (NGS), including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNAseq), on clinical samples from patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) could aid in comprehending tumorigenesis, genetic and genomic heterogeneity, as well as developing molecular classifications for specialized targeted therapy...
July 17, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28706762/metastatic-breast-cancer-with-brca-mutation-discovered-by-next-generation-sequencing-responding-to-olaparib
#11
Wajeeha Rizvi, Phu Truong, Quoc Truong
Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) mutations are associated with hereditary breast and ovarian cancer syndromes (HBOC). However, certain individuals with breast cancer do not meet high-risk factors for hereditary breast cancer screening based on age, family history, and biology of malignancy. We present a patient with relapsed breast cancer who developed progressive disease with significant tumor burden causing a recurrent pleural effusion. Next-generation sequencing (NGS) done on a tumor biopsy was positive for the BRCA2 mutation...
June 11, 2017: Curēus
https://www.readbyqxmd.com/read/28696559/genetic-testing-for-hereditary-nonpolyposis-colorectal-cancer-hnpcc
#12
Babi Ramesh Reddy Nallamilli, Madhuri Hegde
Hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome, is an autosomal dominant cancer syndrome that confers an elevated risk of early-onset colorectal cancer (CRC) and increased lifetime risk for other cancers of the endometrium, stomach, small intestine, hepatobiliary system, kidney, ureter, and ovary. Lynch syndrome accounts for up to 3% of all CRC, making it the most common hereditary colorectal cancer syndrome. Germline mutations in methyl-directed mismatch repair (MMR) genes give rise to microsatellite instability (MSI) in tumor DNA...
July 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28693197/recent-developments-in-predictive-biomarkers-of-pediatric-glioma
#13
Zhengwei Li, Yiyu Yin, Fengli Liu
The presence of certain cancer-related genetic and epigenetic alterations in the tumor affects patient response to specific cancer therapies. The accurate screening of these predictive biomarkers in molecular diagnostics is important since it enables the tailoring of optimal treatment based on molecular characteristics of the tumor. We searched the electronic database PubMed for preclinical as well as clinical controlled trials reporting on various multiple predictors of glioma. It was observed clearly that multiple approaches are evolving and a few of them have also shown promising results...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28685435/hypoxia-related-tumor-acidosis-affects-microrna-expression-pattern-in-prostate-and-breast-tumor-cells
#14
A Riemann, S Reime, O Thews
MicroRNAs (miRNAs) are small non-coding RNA sequences which are able to modulate the expression of many functional proteins. The expression level of miRNAs can be modulated by parameters of the tumor microenvironment like hypoxia, nutrient deprivation or oxidative stress. Since miRNAs can act either as oncogenes or tumor suppressors, this may affect malignant progression or therapy resistance. In the present study it was analyzed whether extracellular acidosis can impact on miRNA expression. Therefore, tumor cells (R3327-AT-1 prostate and Walker-256 mammary carcinoma cells) were incubated at pH 6...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28685087/heterogeneity-in-the-colorectal-primary-tumor-and-the-synchronous-resected-liver-metastases-prior-to-and-after-treatment-with-an-anti-egfr-monoclonal-antibody
#15
Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28683819/interpreting-whole-genome-and-exome-sequencing-data-of-individual-gastric-cancer-samples
#16
Daniela Esser, Niklas Holze, Jochen Haag, Stefan Schreiber, Sandra Krüger, Viktoria Warneke, Philip Rosenstiel, Christoph Röcken
BACKGROUND: Gastric cancer is the fourth most common cancer and the second leading cause of cancer death worldwide. In order to understand the genetic background, we sequenced the whole exome and the whole genome of one microsatellite stable as well as one microsatellite unstable tumor and the matched healthy tissue on two different NGS platforms. We here aimed to provide a comparative approach for individual clinical tumor sequencing and annotation using different sequencing technologies and mutation calling algorithms...
July 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28683468/correlation-between-circulating-mutant-dna-and-metabolic-tumour-burden-in-advanced-non-small-cell-lung-cancer-patients
#17
Anne Winther-Larsen, Christina Demuth, Joan Fledelius, Anne Tranberg Madsen, Karin Hjorthaug, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival. METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28681041/next-generation-sequencing-reveals-potentially-actionable-alterations-in-the-majority-of-patients-with-lymphoid-malignancies
#18
Aaron M Goodman, Michael Choi, Matthew Wieduwilt, Carolyn Mulroney, Caitlin Costello, Garrett Frampton, Vincent Miller, Razelle Kurzrock
Next generation sequencing (NGS) identifies alterations that may be potentially targetable by Food and Drug Administration (FDA) approved drugs and/or by available experimental agents that may not have otherwise been contemplated. Many targeted drugs have been developed for diverse solid cancers; a smaller number of genomically targeted drugs have been approved for lymphoid malignancies. We analyzed NGS results from 60 patients with various lymphoid malignancies and found a total of 224 alterations (median per patient = 3)...
June 2017: JCO Precis Oncol
https://www.readbyqxmd.com/read/28675654/bioinformatory-assisted-analysis-of-next-generation-sequencing-data-for-precision-medicine-in-pancreatic-cancer
#19
Linnéa Malgerud, Johan Lindberg, Valtteri Wirta, Maria Gustafsson-Liljefors, Masoud Karimi, Carlos Fernández Moro, Katrin Stecker, Alexander Picker, Carolin Huelsewig, Martin Stein, Regina Bohnert, Marco Del Chiaro, Stephan L Haas, Rainer L Heuchel, Johan Permert, Markus J Maeurer, Stephan Brock, Caroline S Verbeke, Lars Engstrand, David B Jackson, Henrik Grönberg, J-Matthias Löhr
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly due to chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes Next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity...
July 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28675028/egfr-and-cd44-dual-targeted-multifunctional-hyaluronic-acid-nanogels-boost-protein-delivery-to-ovarian-and-breast-cancers-in-vitro-and-in-vivo
#20
Jing Chen, Jia Ouyang, Qijun Chen, Chao Deng, Fenghua Meng, Jian Zhang, Ru Cheng, Qing Lan, Zhiyuan Zhong
Protein drugs with intracellular targets like Granzyme B (GrB) have demonstrated great proliferative inhibition activity in cancer cells. Their clinical translation, however, relies on the development of safe, efficient, and selective protein-delivery vehicles. Here, we report that epidermal growth factor receptor (EGFR) and CD44 dual-targeted multifunctional hyaluronic acid nanogels (EGFR/CD44-NGs) boost protein delivery to ovarian and breast cancers in vitro and in vivo. EGFR/CD44-NGs obtained via nanoprecipitation and photoclick chemistry from hyaluronic acid derivatives with tetrazole, GE11 peptide/tetrazole, and cystamine methacrylate groups had nearly quantitative loading of therapeutic proteins like cytochrome C (CC) and GrB, a small size of ca...
July 19, 2017: ACS Applied Materials & Interfaces
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