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Genomic instability cancer

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https://www.readbyqxmd.com/read/29232465/new-treatments-in-ovarian-cancer
#1
E Pujade-Lauraine
In targeting DNA repair pathways of the most genomic instable cancer, poly-(adenosine diphosphate [ADP])-ribose polymerase inhibitors (PARPi) have been demonstrated as the most effective drug since platinum in high grade serous or endometrioid ovarian cancer. Immunotherapy is strongly pushing the door of ovarian cancer and has the ambition to change the fate of this deadly disease when combined with chemotherapy, vascular endothelial growth factor inhibitor or PARPi. The activity of PARPi could also be improved by modulators of the cell cycle, which are required to give time enough for DNA repair...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29231811/genome-wide-mapping-of-sister-chromatid-exchange-events-in-single-yeast-cells-using-strand-seq
#2
Clémence Claussin, David Porubský, Diana Cj Spierings, Nancy Halsema, Stefan Rentas, Victor Guryev, Peter M Lansdorp, Michael Chang
Homologous recombination involving sister chromatids is the most accurate, and thus most frequently used, form of recombination-mediated DNA repair. Despite its importance, sister chromatid recombination is not easily studied because it does not result in a change in DNA sequence, making recombination between sister chromatids difficult to detect. We have previously developed a novel DNA template strand sequencing technique, called Strand-seq, that can be used to map sister chromatid exchange (SCE) events genome-wide in single cells...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29230882/molecular-profiling-and-genome-wide-analysis-based-on-somatic-copy-number-alterations-in-advanced-colorectal-cancers
#3
Tamotsu Sugai, Yayoi Takahashi, Makoto Eizuka, Ryo Sugimoto, Yasuko Fujita, Wataru Habano, Kouki Otsuka, Akira Sasaki, Eiichiro Yamamoto, Takayuki Matsumoto, Hiromu Suzuki
To characterize somatic alterations in colorectal cancer (CRC), we conducted a genome-scale analysis of 106 CRC specimens. We assessed comprehensive somatic copy number alterations (SCNAs) in these CRC specimens. In addition, we examined microsatellite instability (MSI; low and high), genetic mutations (KRAS, BRAF, TP53, and PIK3CA), and DNA methylation status (classified into low, intermediate, and high type). We stratified molecular alterations in the CRCs using a hierarchical cluster analysis. The examined CRCs could be categorized into 3 subgroups using hierarchical cluster analysis...
December 12, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29228717/somatic-prdm2-c-4467dela-mutations-in-colorectal-cancers-control-histone-methylation-and-tumor-growth
#4
Tatjana Pandzic, Veronica Rendo, Jinyeong Lim, Chatarina Larsson, Jimmy Larsson, Ivaylo Stoimenov, Snehangshu Kundu, Muhammad Akhtar Ali, Mats Hellström, Liqun He, Anders M Lindroth, Tobias Sjöblom
The chromatin modifier PRDM2/RIZ1 is inactivated by mutation in several forms of cancer and is a putative tumor suppressor gene. Frameshift mutations in the C-terminal region of PRDM2, affecting (A)8 or (A)9 repeats within exon 8, are found in one third of colorectal cancers with microsatellite instability, but the contribution of these mutations to colorectal tumorigenesis is unknown. To model somatic mutations in microsatellite unstable tumors, we devised a general approach to perform genome editing while stabilizing the mutated nucleotide repeat...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212891/bypassing-border-control-nuclear-envelope-rupture-in-disease
#5
REVIEW
Gaëlle Houthaeve, Joke Robijns, Kevin Braeckmans, Winnok H De Vos
Recent observations in laminopathy patient cells and cancer cells have revealed that the nuclear envelope (NE) can transiently rupture during interphase. NE rupture leads to an uncoordinated exchange of nuclear and cytoplasmic material, thereby deregulating cellular homeostasis. Moreover, concurrently inflicted DNA damage could prime rupture-prone cells for genome instability. Thus, NE rupture may represent a novel pathogenic mechanism that has far-reaching consequences for cell and organism physiology.
January 1, 2018: Physiology
https://www.readbyqxmd.com/read/29212265/systematic-identification-of-long-non-coding-rnas-with-cancer-testis-expression-patterns-in-14-cancer-types
#6
Na Qin, Cheng Wang, Qun Lu, Zijian Ma, Juncheng Dai, Hongxia Ma, Guangfu Jin, Hongbing Shen, Zhibin Hu
Cancer-testis (CT) genes are a group of genes that are potential targets of immunotherapy and candidate epi-drivers participating in the development of cancers. Previous studies mainly focused on protein-coding genes, neglecting long non-coding RNAs with the same expression patterns. In this study, we performed a systematic investigation of cancer-testis long non-coding RNAs (CT-lncRNAs) with multiple independent open-access databases.We identified 1,325 extremely highly expressed CT-lncRNAs (EECT-lncRNAs) in 14 cancer types...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212152/prpf8-is-important-for-brca1-mediated-homologous-recombination
#7
David O Onyango, Gabriella Lee, Jeremy M Stark
Disruption of RNA splicing causes genome instability, which could contribute to cancer etiology. Furthermore, RNA splicing is an emerging anti-cancer target. Thus, we have evaluated the influence of the spliceosome factor PRPF8 and the splicing inhibitor Pladienolide B (PlaB) on homologous recombination (HR). We find that PRPF8 depletion and PlaB treatment cause a specific defect in homology-directed repair (HDR), and single strand annealing (SSA), which share end resection as a common intermediate, and BRCA1 as a required factor...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209918/molecular-classification-and-precision-therapy-of-cancer-immune-checkpoint-inhibitors
#8
Yingyan Yu
On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers...
December 5, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/29207595/cdk1-promotes-nascent-dna-synthesis-and-induces-resistance-of-cancer-cells-to-dna-damaging-therapeutic-agents
#9
Hongwei Liao, Fang Ji, Xinwei Geng, Meichun Xing, Wen Li, Zhihua Chen, Huahao Shen, Songmin Ying
Cyclin dependent kinase 1 (CDK1) is essential for cell viability and plays a vital role in many biological events including cell cycle control, DNA damage repair, and checkpoint activation. Here, we identify an unanticipated role for CDK1 in promoting nascent DNA synthesis during S-phase. We report that a short duration of CDK1 inhibition, which does not perturb cell cycle progression, triggers a replication-associated DNA damage response (DDR). This DDR is associated with a disruption of replication fork progression and leads to genome instability...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29204983/phyllanthus-emblica-linn-fruit-extract-potentiates-the-anticancer-efficacy-of-mitomycin-c-and-cisplatin-and-reduces-their-genotoxicity-to-normal-cells-in-vitro
#10
Xi-Han Guo, Juan Ni, Jing-Lun Xue, Xu Wang
OBJECTIVE: Fruit of Phyllanthus emblica Linn. (PE) is widely consumed as a functional food and used as a folk medicine due to its remarkable nutritional and pharmacological effects. Mitomycin C (MMC) and cisplatin (cDDP) are the most widely used forms of chemotherapeutic drug, but their clinical use is limited by their genotoxicity to normal cells. We aimed to determine whether PE has potential to reduce the genotoxicity, while improving the anticancer effect, of MMC and cDDP. METHODS: Cell proliferation was evaluated using the trypan blue exclusion assay and colony-forming assay...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29203974/deterministic-role-of-cea-and-msi-status-in-predicting-outcome-of-crc-patients-a-perspective-study-amongst-hospital-attending-eastern-indian-populations
#11
Banerjee Koyel, Das Priyabrata, Bhattacharya Rittwika, Dasgupta Swati, Mukhopadhyay Soma, Basak Jayasri, Mukhopadhyay Ashis
Carcinoembryonic antigen (CEA) is an important deterministic factor in predicting colorectal carcinoma (CRC) progression. It is also evident that microsatellite instability (MSI) which results in a hypermutable phenotype of genomic DNA is common in CRC. Owing to the scarcity of reports from India, our aim of this study was to understand the clinicopathological correlations of CEA status with surgery and chemotherapy, correlate the same with socio-demographic status of the patients, determine the MSI status amongst them and understand the prognostic implications of CEA and MSI as CRC progression marker amongst patients...
December 2017: Indian Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29202485/selenite-restores-pax6-expression-in-neuronal-cells-of-chronically-arsenic-exposed-golden-syrian-hamsters
#12
Alain Aguirre-Vázquez, Adriana Sampayo-Reyes, Laura González-Escalante, Alba Hernández, Ricard Marcos, Fabiola Castorena-Torres, Gerardo Lozano-Garza, Reyes Taméz-Guerra, Mario Bermúdez de León
Arsenic is a worldwide environmental pollutant that generates public health concerns. Various types of cancers and other diseases, including neurological disorders, have been associated with human consumption of arsenic in drinking water. At the molecular level, arsenic and its metabolites have the capacity to provoke genome instability, causing altered expression of genes. One such target of arsenic is the Pax6 gene that encodes a transcription factor in neuronal cells. The aim of this study was to evaluate the effect of two antioxidants, α-tocopheryl succinate (α-TOS) and sodium selenite, on Pax6 gene expression levels in the forebrain and cerebellum of Golden Syrian hamsters chronically exposed to arsenic in drinking water...
December 5, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/29192902/relevance-of-the-p53-mdm2-axis-to-aging
#13
REVIEW
Danyi Wu, Carol Prives
In response to varying stress signals, the p53 tumor suppressor is able to promote repair, survival, or elimination of damaged cells - processes that have great relevance to organismal aging. Although the link between p53 and cancer is well established, the contribution of p53 to the aging process is less clear. Delineating how p53 regulates distinct aging hallmarks such as cellular senescence, genomic instability, mitochondrial dysfunction, and altered metabolic pathways will be critical. Mouse models have further revealed the centrality and complexity of the p53 network in aging processes...
December 1, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29192276/protein-lysine-methyltransferases-g9a-and-glp1-promote-responses-to-dna-damage
#14
Vasudeva Ginjala, Lizahira Rodriguez-Colon, Bratati Ganguly, Prawallika Gangidi, Paul Gallina, Husam Al-Hraishawi, Atul Kulkarni, Jeremy Tang, Jinesh Gheeya, Srilatha Simhadri, Ming Yao, Bing Xia, Shridar Ganesan
Upon induction of DNA breaks, ATM activation leads to a cascade of local chromatin modifications that promote efficient recruitment of DNA repair proteins. Errors in this DNA repair pathway lead to genomic instability and cancer predisposition. Here, we show that the protein lysine methyltransferase G9a (also known as EHMT2) and GLP1 (also known as EHMT1) are critical components of the DNA repair pathway. G9a and GLP1 rapidly localizes to DNA breaks, with GLP1 localization being dependent on G9a. ATM phosphorylation of G9a on serine 569 is required for its recruitment to DNA breaks...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190829/a-comprehensive-analysis-of-breast-cancer-microbiota-and-host-gene-expression
#15
Kevin J Thompson, James N Ingle, Xiaojia Tang, Nicholas Chia, Patricio R Jeraldo, Marina R Walther-Antonio, Karunya K Kandimalla, Stephen Johnson, Janet Z Yao, Sean C Harrington, Vera J Suman, Liewei Wang, Richard L Weinshilboum, Judy C Boughey, Jean-Pierre Kocher, Heidi Nelson, Matthew P Goetz, Krishna R Kalari
The inflammatory tumoral-immune response alters the physiology of the tumor microenvironment, which may attenuate genomic instability. In addition to inducing inflammatory immune responses, several pathogenic bacteria produce genotoxins. However the extent of microbial contribution to the tumor microenvironment biology remains unknown. We utilized The Cancer Genome Atlas, (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence to minimize laboratory costs and effort...
2017: PloS One
https://www.readbyqxmd.com/read/29182103/association-of-mitochondrial-copy-number-variation-and-t16189c-polymorphism-with-colorectal-cancer-in-north-indian-population
#16
Bhupender Kumar, Zafar Iqbal Bhat, Savita Bansal, Sunil Saini, Afreen Naseem, Khushnuma Wahabi, Archana Burman, Geeta Trilok Kumar, Sundeep Singh Saluja, M Moshahid Alam Rizvi
Globally, colorectal cancer is the third most common type of cancer. Genetic instability leading to cancer development is one of the major causes for development of cancer. Alterations in mitochondrial genome, that is, mutations, single-nucleotide polymorphisms, and copy number variations are known to contribute in cancer development. The aim of our study was to investigate association of mitochondrial T16189C polymorphism and copy number variation with colorectal cancer in North Indian population. DNA isolated from peripheral blood of 126 colorectal cancer patients and 114 healthy North Indian subjects was analyzed for T16189C polymorphism and half of them for mitochondrial copy number variation...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29181861/aneuploidy-tp53-mutation-and-amplification-of-myc-correlate-with-increased-intratumor-heterogeneity-and-poor-prognosis-of-breast-cancer-patients
#17
Johanna Oltmann, Kerstin Heselmeyer-Haddad, Leanora S Hernandez, Rüdiger Meyer, Irianna Torres, Yue Hu, Natalie Doberstein, J Keith Killian, David Petersen, Y Jack Zhu, Daniel C Edelman, Paul S Meltzer, Russell Schwartz, E Michael Gertz, Alejandro A Schäffer, Gert Auer, Jens K Habermann, Thomas Ried
The clinical course of breast cancer varies from one patient to another. Currently, the choice of therapy relies on clinical parameters and histological and molecular tumor features. Alas, these markers are informative in only a subset of patients. Therefore, additional predictors of disease outcome would be valuable for treatment stratification. Extensive studies showed that the degree of variation of the nuclear DNA content, i.e., aneuploidy determines prognosis. Our aim was to further elucidate the molecular basis of aneuploidy...
November 27, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29176630/break-induced-replication-promotes-formation-of-lethal-joint-molecules-dissolved-by-srs2
#18
Rajula Elango, Ziwei Sheng, Jessica Jackson, Jenna DeCata, Younis Ibrahim, Nhung T Pham, Diana H Liang, Cynthia J Sakofsky, Alessandro Vindigni, Kirill S Lobachev, Grzegorz Ira, Anna Malkova
Break-induced replication (BIR) is a DNA double-strand break repair pathway that leads to genomic instabilities similar to those observed in cancer. BIR proceeds by a migrating bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains unknown how this ssDNA is prevented from unscheduled pairing with the template, which can lead to genomic instability. Here, we propose that uncontrolled Rad51 binding to this ssDNA promotes formation of toxic joint molecules that are counteracted by Srs2...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29174566/the-roles-of-pathology-in-targeted-therapy-of-women-with-gynecologic-cancers
#19
Rajmohan Murali, Rachel N Grisham, Robert A Soslow
The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor...
November 23, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29173760/targeting-dna-damage-in-sclc
#20
REVIEW
Victoria Foy, Maximilian W Schenk, Katie Baker, Fabio Gomes, Alice Lallo, Kristopher K Frese, Martin Forster, Caroline Dive, Fiona Blackhall
SCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's. The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability...
December 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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