keyword
MENU ▼
Read by QxMD icon Read
search

Genomic instability cancer

keyword
https://www.readbyqxmd.com/read/28445142/potential-biomarkers-of-dna-replication-stress-in-cancer
#1
Liqun Ren, Long Chen, Wei Wu, Lorenza Garribba, Huanna Tian, Zihui Liu, Ivan Vogel, Chunhui Li, Ian D Hickson, Ying Liu
Oncogene activation is an established driver of tumorigenesis. An apparently inevitable consequence of oncogene activation is the generation of DNA replication stress (RS), a feature common to most cancer cells. RS, in turn, is a causal factor in the development of chromosome instability (CIN), a near universal feature of solid tumors. It is likely that CIN and RS are mutually reinforcing drivers that not only accelerate tumorigenesis, but also permit cancer cells to adapt to diverse and hostile environments...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445112/tracking-the-evolution-of-non-small-cell-lung-cancer
#2
Mariam Jamal-Hanjani, Gareth A Wilson, Nicholas McGranahan, Nicolai J Birkbak, Thomas B K Watkins, Selvaraju Veeriah, Seema Shafi, Diana H Johnson, Richard Mitter, Rachel Rosenthal, Max Salm, Stuart Horswell, Mickael Escudero, Nik Matthews, Andrew Rowan, Tim Chambers, David A Moore, Samra Turajlic, Hang Xu, Siow-Ming Lee, Martin D Forster, Tanya Ahmad, Crispin T Hiley, Christopher Abbosh, Mary Falzon, Elaine Borg, Teresa Marafioti, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Rajesh Shah, Leena Joseph, Anne M Quinn, Phil A Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Stefan Dentro, Philippe Taniere, Brendan O'Sullivan, Helen L Lowe, John A Hartley, Natasha Iles, Harriet Bell, Yenting Ngai, Jacqui A Shaw, Javier Herrero, Zoltan Szallasi, Roland F Schwarz, Aengus Stewart, Sergio A Quezada, John Le Quesne, Peter Van Loo, Caroline Dive, Allan Hackshaw, Charles Swanton
Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. Methods In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy...
April 26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28439615/wip1-phosphatase-as-pharmacological-target-in-cancer-therapy
#3
REVIEW
Soňa Pecháčková, Kamila Burdová, Libor Macurek
DNA damage response (DDR) pathway protects cells from genome instability and prevents cancer development. Tumor suppressor p53 is a key molecule that interconnects DDR, cell cycle checkpoints, and cell fate decisions in the presence of genotoxic stress. Inactivating mutations in TP53 and other genes implicated in DDR potentiate cancer development and also influence the sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of DDR and has been proposed as potential pharmaceutical target...
April 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28438622/p53-alteration-in-morphologically-normal-benign-breast-luminal-cells-in-brca-carriers-with-or-without-history-of-breast-cancer
#4
Xi Wang, Amber A El-Halaby, Hengwei Zhang, Qi Yang, Todd S Laughlin, Paul G Rothberg, Kristin Skinner, David G Hicks
Germ-line mutations in BRCA genes have been shown to predispose patients to breast cancer. Studies have suggested that p53 alteration is a necessary step in tumorigenesis in BRCA carriers. Our previous study showed p53 alteration in morphologically normal/benign breast luminal cells in sporadic breast cancer patients, the so-called "breast p53 signature". Here, we studied p53 status in 66 BRCA1/2 carriers' breasts; 29 patients with breast carcinoma (2 patients with bilateral breast carcinomas) and 37 without...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28436987/genomic-consequences-of-aberrant-dna-repair-mechanisms-stratify-ovarian-cancer-histotypes
#5
Yi Kan Wang, Ali Bashashati, Michael S Anglesio, Dawn R Cochrane, Diljot S Grewal, Gavin Ha, Andrew McPherson, Hugo M Horlings, Janine Senz, Leah M Prentice, Anthony N Karnezis, Daniel Lai, Mohamed R Aniba, Allen W Zhang, Karey Shumansky, Celia Siu, Adrian Wan, Melissa K McConechy, Hector Li-Chang, Alicia Tone, Diane Provencher, Manon de Ladurantaye, Hubert Fleury, Aikou Okamoto, Satoshi Yanagida, Nozomu Yanaihara, Misato Saito, Andrew J Mungall, Richard Moore, Marco A Marra, C Blake Gilks, Anne-Marie Mes-Masson, Jessica N McAlpine, Samuel Aparicio, David G Huntsman, Sohrab P Shah
We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28435051/akt1-nf%C3%AE%C2%BAb-signaling-pathway-activation-by-a-small-molecule-dma-confers-radioprotection-to-intestinal-epithelium-in-xenograft-model
#6
Vinod Tiwari, Mohammad Zahid Kamran, Atul Ranjan, Hemlata Nimesh, Manish Singh, Vibha Tandon
Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28432052/genomic-instability-in-cancer-teetering-on-the-limit-of-tolerance
#7
REVIEW
Noemi Andor, Carlo C Maley, Hanlee P Ji
Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold...
April 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28431273/chromosomal-instability-in-gastric-cancer-biology
#8
REVIEW
Saffiyeh Saboor Maleki, Christoph Röcken
Gastric cancer (GC) is the fifth most common cancer in the world and accounts for 7% of the total cancer incidence. The prognosis of GC is dismal in Western countries due to late diagnosis: approximately 70% of the patients die within 5 years following initial diagnosis. Recently, integrative genomic analyses led to the proposal of a molecular classification of GC into four subtypes, i.e.,microsatellite-instable, Epstein-Barr virus-positive, chromosomal-instable (CIN), and genomically stable GCs. Molecular classification of GC advances our knowledge of the biology of GC and may have implications for diagnostics and patient treatment...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28427283/break-induced-replication-in-eukaryotes-mechanisms-functions-and-consequences
#9
Cynthia J Sakofsky, Anna Malkova
Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA...
April 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28426752/somatic-copy-number-alterations-in-gastric-adenocarcinomas-among-asian-and-western-patients
#10
Steven E Schumacher, Byoung Yong Shim, Giovanni Corso, Min-Hee Ryu, Yoon-Koo Kang, Franco Roviello, Gordon Saksena, Shouyong Peng, Ramesh A Shivdasani, Adam J Bass, Rameen Beroukhim
Gastric cancer, a leading worldwide cause of cancer mortality, shows high geographic and ethnic variation in incidence rates, which are highest in East Asia. The anatomic locations and clinical behavior also differ by geography, leading to the controversial idea that Eastern and Western forms of the disease are distinct. In view of these differences, we investigated whether gastric cancers from Eastern and Western patients show distinct genomic profiles. We used high-density profiling of somatic copy-number aberrations to analyze the largest collection to date of gastric adenocarcinomas and utilized genotyping data to rigorously annotate ethnic status...
2017: PloS One
https://www.readbyqxmd.com/read/28425536/cisplatin-resistance-in-cell-models-evaluation-of-metallomic-and-biological-predictive-biomarkers-to-address-early-therapy-failure
#11
Marta Espina, Mario Corte-Rodríguez, Leticia Aguado, María Montes-Bayón, Marta I Sierra, Pablo Martínez-Camblor, Elisa Blanco-González, L María Sierra
Cisplatin, one of the most extensively used metallodrugs in cancer treatment, presents the important drawback of patient resistance. This resistance is the consequence of different processes including those preventing the formation of DNA adducts and/or their quick removal. Thus, a tool for the accurate detection and quantitation of cisplatin-induced adducts might be valuable for predicting patient resistance. To prove the validity of such an assumption, highly sensitive plasma mass spectrometry (ICP-MS) strategies were applied to determine DNA adduct levels and intracellular Pt concentrations...
April 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28423708/targeting-the-centriolar-replication-factor-stil-synergizes-with-dna-damaging-agents-for-treatment-of-ovarian-cancer
#12
Noa Rabinowicz, Lingegowda S Mangala, Kevin R Brown, Cintia Checa-Rodriguez, Asher Castiel, Oren Moskovich, Giulia Zarfati, Luba Trakhtenbrot, Adva Levy-Barda, Dahai Jiang, Cristian Rodriguez-Aguayo, Sunila Pradeep, Yael van Praag, Gabriel Lopez-Berestein, Ahuvit David, Ilya Novikov, Pablo Huertas, Robert Rottapel, Anil K Sood, Shai Izraeli
Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422758/first-in-human-trial-of-multikinase-vegf-inhibitor-regorafenib-and-anti-egfr-antibody-cetuximab-in-advanced-cancer-patients
#13
Vivek Subbiah, Muhammad Rizwan Khawaja, David S Hong, Behrang Amini, Jiang Yungfang, Hui Liu, Adrienne Johnson, Alexa B Schrock, Siraj M Ali, James X Sun, David Fabrizio, Sarina Piha-Paul, Siqing Fu, Apostolia M Tsimberidou, Aung Naing, Filip Janku, Daniel D Karp, Michael Overman, Cathy Eng, Scott Kopetz, Funda Meric-Bernstam, Gerald S Falchook
BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR-sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC). METHODS: Utilizing a standard 3+3 design, a phase I study was designed to determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) of the regorafenib plus cetuximab combination among patients with advanced cancer including CRC...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28421114/status-of-epstein-barr-virus-coinfection-with-helicobacter-pylori-in-gastric-cancer
#14
REVIEW
Shyam Singh, Hem Chandra Jha
Epstein-Barr virus is a ubiquitous human herpesvirus whose primary infection causes mononucleosis, Burkett's lymphoma, nasopharyngeal carcinoma, autoimmune diseases, and gastric cancer (GC). The persistent infection causes malignancies in lymph and epithelial cells. Helicobacter pylori causes gastritis in human with chronic inflammation. This chronic inflammation is thought to be the cause of genomic instability. About 45%-word population have a probability of having both pathogens, namely, H. pylori and EBV...
2017: Journal of Oncology
https://www.readbyqxmd.com/read/28420421/analysis-of-100-000-human-cancer-genomes-reveals-the-landscape-of-tumor-mutational-burden
#15
Zachary R Chalmers, Caitlin F Connelly, David Fabrizio, Laurie Gay, Siraj M Ali, Riley Ennis, Alexa Schrock, Brittany Campbell, Adam Shlien, Juliann Chmielecki, Franklin Huang, Yuting He, James Sun, Uri Tabori, Mark Kennedy, Daniel S Lieber, Steven Roels, Jared White, Geoffrey A Otto, Jeffrey S Ross, Levi Garraway, Vincent A Miller, Phillip J Stephens, Garrett M Frampton
BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. METHODS: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome...
April 19, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28420124/applying-broadband-dielectric-spectroscopy-bds-for-the-biophysical-characterization-of-mammalian-tissues-under-a-variety-of-cellular-stresses
#16
Maria P Souli, Panagiotis Klonos, Adamantia F Fragopoulou, Ifigeneia V Mavragani, Ioannis S Pateras, Nikolaos Kostomitsopoulos, Lukas H Margaritis, Pavlos Zoumpoulis, Loukas Kaklamanis, Dimitris Kletsas, Vassilis G Gorgoulis, Apostolos Kyritsis, Polycarpos Pissis, Alexandros G Georgakilas
The dielectric properties of biological tissues can contribute non-invasively to a better characterization and understanding of the structural properties and physiology of living organisms. The question we asked, is whether these induced changes are effected by an endogenous or exogenous cellular stress, and can they be detected non-invasively in the form of a dielectric response, e.g., an AC conductivity switch in the broadband frequency spectrum. This study constitutes the first methodological approach for the detection of environmental stress-induced damage in mammalian tissues by the means of broadband dielectric spectroscopy (BDS) at the frequencies of 1-10⁶ Hz...
April 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28415565/rad52-deficiency-decreases-development-of-lung-squamous-cell-carcinomas-by-enhancing-immuno-surveillance
#17
Rachel Lieberman, Jing Pan, Qi Zhang, Ming You
RAD52 is involved in homologous recombination and DNA repair. This study focuses on lung cancer progression and how the DNA repair gene, Rad52, enables tumor cells to have sufficient genome integrity, i.e., the ability to repair lethal DNA damage, to avoid cell death. In this report, we analyze the phenotypic differences between wild type and Rad52-/- in inhibition of tumor phenotypes including cell growth, viability, cytolysis, and immune profiling. We demonstrated that loss of Rad52 not only increases the death of cells undergoing carcinogen-induced transformation in vivo, but that Rad52 loss also augments in vivo antitumor activity through an enhanced capacity for direct killing of LLC tumor cells by stimulated Rad52-/- NK and CD8+ T cells...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412752/clinicopathologic-implications-of-immune-classification-by-pd-l1-expression-and-cd8-positive-tumor-infiltrating-lymphocytes-in-stage-ii-and-iii-gastric-cancer-patients
#18
Jiwon Koh, Chan-Young Ock, Jin Won Kim, Soo Kyung Nam, Yoonjin Kwak, Sumi Yun, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee
We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in gastric cancer (GC), and categorized into 4 microenvironment immune types. Immunohistochemistry (PD-L1, CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based adjuvant chemotherapy, and two public genome databases were analyzed for validation. PD-L1+ was found in 98/392 GCs (25...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411036/prolonged-particulate-chromate-exposure-does-not-inhibit-homologous-recombination-repair-in-north-atlantic-right-whale-eubalaena-glacialis-lung-cells
#19
Cynthia L Browning, Catherine F Wise, John Pierce Wise
Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability...
April 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28410206/development-of-diagnostic-scar-markers-for-genomic-dna-amplifications-in-breast-carcinoma-by-dna-cloning-of-high-gc-ramp-pcr-fragments
#20
Shangyi Fu, Jingliang Cheng, Chunli Wei, Luquan Yang, Xiuli Xiao, Dianzheng Zhang, M David Stewart, Junjiang Fu
Cancer is genetically heterogeneous regarding to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers, including DNA markers, is used in determining genomic instability, molecular subtype determination and disease prognosis, and estimating sensitivity to different drugs in clinical practice. In a previous study, we developed highly effective DNA markers using improved random amplified polymorphic DNA (RAPD) with high-GC primers, which is a valuable approach for the genetic authentication of medicinal plants...
March 30, 2017: Oncotarget
keyword
keyword
104874
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"