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Genomic instability cancer

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https://www.readbyqxmd.com/read/29454317/oxidative-damage-and-response-to-bacillus-calmette-gu%C3%A3-rin-in-bladder-cancer-cells-expressing-sialyltransferase-st3gal1
#1
Paulo F Severino, Mariana Silva, Mylene Carrascal, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Roberto Barbaro Forleo, Annalisa Astolfi, Mariangela Catera, Paula A Videira, Fabio Dall'Olio
BACKGROUND: Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients. NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown. METHODS: The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T , that express, respectively, either the sT or the T antigens...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29454225/low-power-lasers-on-genomic-stability
#2
Larissa Alexsandra da Silva Neto Trajano, Luiz Philippe da Silva Sergio, Ana Carolina Stumbo, Andre Luiz Mencalha, Adenilson de Souza da Fonseca
Exposure of cells to genotoxic agents causes modifications in DNA, resulting to alterations in the genome. To reduce genomic instability, cells have DNA damage responses in which DNA repair proteins remove these lesions. Excessive free radicals cause DNA damages, repaired by base excision repair and nucleotide excision repair pathways. When non-oxidative lesions occur, genomic stability is maintained through checkpoints in which the cell cycle stops and DNA repair occurs. Telomere shortening is related to the development of various diseases, such as cancer...
February 10, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29452566/near-tetraploid-cancer-cells-show-chromosome-instability-triggered-by-replication-stress-and-exhibit-enhanced-invasiveness
#3
Darawalee Wangsa, Isabel Quintanilla, Keyvan Torabi, Maria Vila-Casadesús, Amaia Ercilla, Gregory Klus, Zeynep Yuce, Claudia Galofré, Miriam Cuatrecasas, Juan José Lozano, Neus Agell, Daniela Cimini, Antoni Castells, Thomas Ried, Jordi Camps
A considerable proportion of tumors exhibit aneuploid karyotypes, likely resulting from the progressive loss of chromosomes after whole-genome duplication. Here, by using isogenic diploid and near-tetraploid (4N) single-cell-derived clones from the same parental cell lines, we aimed at exploring how polyploidization affects cellular functions and how tetraploidy generates chromosome instability. Gene expression profiling in 4N clones revealed a significant enrichment of transcripts involved in cell cycle and DNA replication...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29447627/lynch-syndrome-and-muir-torre-syndrome-an-update-and-review-on-the-genetics-epidemiology-and-management-of-two-related-disorders
#4
Stephanie Le, Umer Ansari, Aisha Mumtaz, Kunal Malik, Parth Patel, Amanda Doyle, Amor Khachemoune
Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is an autosomal dominant, tumor predisposing disorder usuallycaused by germline mutations in mismatch repair (MMR) genes. A subset of HNPCC, Muir-Torre Syndrome (MTS) also involves MMR gene defects and is generally accepted as a variant of HNPCC. MTS is typicallycharacterized by at least one visceral malignancy and one cutaneous neoplasm of sebaceous differentiation, with or without keratoacanthomas. In either version of the disorder, nonfunctional MMR systems lead tothe loss of genomic integrity, marked commonly by mismatches in repetitive DNA sequences, resulting in microsatellite instabilities...
November 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/29443391/human-papillomavirus-genome-integration-in-squamous-carcinogenesis-what-have-next-generation-sequencing-studies-taught-us
#5
REVIEW
Ian J Groves, Nicholas Coleman
Human papillomavirus (HPV) infection is associated with ~5% of all human cancers, including a range of squamous cell carcinomas (SCCs). Persistent infection by high-risk HPVs (HRHPVs) is associated with the integration of virus genomes (which are usually stably maintained as extrachromosomal episomes) into host chromosomes. Although HRHPV integration rates differ across human sites of infection, this process appears to be an integral event in HPV-associated neoplastic progression, leading to deregulation of virus oncogene expression, host gene expression modulation and further genomic instability...
February 14, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29441648/aggregatibacter-actinomycetemcomitans-infection-causes-dna-double-strand-breaks-in-host-cells
#6
Rie Teshima, Katsuhiro Hanada, Junko Akada, Kenji Kawano, Yoshio Yamaoka
Periodontal disease, an inflammatory disease, is caused by infection with periodontal pathogens. Long-term periodontal disease increases the risk of oral carcinogenesis. Similar to other peptic cancers, oral carcinogenesis also requires multiple genome instabilities; however, the risk factors related to the accumulation of genome instabilities are poorly understood. Here, we suggested that specific periodontal pathogens may increase the risk of genome instability. Accordingly, we screened several periodontal pathogens based on the ability to induce DNA double-strand breaks (DSBs) in host cells...
February 14, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29435136/epigenetic-silencing-of-smoc1-in-traditional-serrated-adenoma-and-colorectal-cancer
#7
Hironori Aoki, Eiichiro Yamamoto, Akira Takasawa, Takeshi Niinuma, Hiro-O Yamano, Taku Harada, Hiro-O Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Yoshihito Tanaka, Yuko Yoshida, Tomoyuki Aoyama, Makoto Eizuka, Akira Yorozu, Hiroshi Kitajima, Masahiro Kai, Norimasa Sawada, Tamotsu Sugai, Hiroshi Nakase, Hiromu Suzuki
Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by BRAF mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including SMOC1 , methylation of which progressively increased during the development of TSAs. SMOC1 was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps ( p < 0...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435132/suppression-of-homology-dependent-dna-double-strand-break-repair-induces-parp-inhibitor-sensitivity-in-vhl-deficient-human-renal-cell-carcinoma
#8
Susan E Scanlon, Denise C Hegan, Parker L Sulkowski, Peter M Glazer
The von Hippel-Lindau ( VHL ) tumor suppressor gene is inactivated in the vast majority of human clear cell renal carcinomas. The pathogenesis of VHL loss is currently best understood to occur through stabilization of the hypoxia-inducible factors, activation of hypoxia-induced signaling pathways, and transcriptional reprogramming towards a pro-angiogenic and pro-growth state. However, hypoxia also drives other pro-tumorigenic processes, including the development of genomic instability via down-regulation of DNA repair gene expression...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29432176/detection-of-aneuploidy-in-patients-with-cancer-through-amplification-of-long-interspersed-nucleotide-elements-lines
#9
Christopher Douville, Simeon Springer, Isaac Kinde, Joshua D Cohen, Ralph H Hruban, Anne Marie Lennon, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Rachel Karchin
Aneuploidy is a feature of most cancer cells, and a myriad of approaches have been developed to detect it in clinical samples. We previously described primers that could be used to amplify ∼38,000 unique long interspersed nucleotide elements (LINEs) from throughout the genome. Here we have developed an approach to evaluate the sequencing data obtained from these amplicons. This approach, called Within-Sample AneupLoidy DetectiOn (WALDO), employs supervised machine learning to detect the small changes in multiple chromosome arms that are often present in cancers...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29429988/the-deubiquitylase-usp15-regulates-topoisomerase-ii-alpha-to-maintain-genome-integrity
#10
Andrew B Fielding, Matthew Concannon, Sarah Darling, Emma V Rusilowicz-Jones, Joseph J Sacco, Ian A Prior, Michael J Clague, Sylvie Urbé, Judy M Coulson
Ubiquitin-specific protease 15 (USP15) is a widely expressed deubiquitylase that has been implicated in diverse cellular processes in cancer. Here we identify topoisomerase II (TOP2A) as a novel protein that is regulated by USP15. TOP2A accumulates during G2 and functions to decatenate intertwined sister chromatids at prophase, ensuring the replicated genome can be accurately divided into daughter cells at anaphase. We show that USP15 is required for TOP2A accumulation, and that USP15 depletion leads to the formation of anaphase chromosome bridges...
February 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29427004/immunohistochemically-detected-idh1r132h-mutation-is-rare-and-mostly-heterogeneous-in-prostate-cancer
#11
Andrea Hinsch, Meta Brolund, Claudia Hube-Magg, Martina Kluth, Ronald Simon, Christina Möller-Koop, Guido Sauter, Stefan Steurer, Andreas Luebke, Alexander Angerer, Corinna Wittmer, Emily Neubauer, Cosima Göbel, Franziska Büscheck, Sarah Minner, Waldemar Wilczak, Thorsten Schlomm, Frank Jacobsen, Till Sebastian Clauditz, Till Krech, Maria Christina Tsourlakis, Cornelia Schroeder
BACKGROUND: IDH1 mutations are oncogenic through induction of DNA damage and genome instability. They are of therapeutic interest because they confer increased sensitivity to radiation and cytotoxic therapy and hold potential for vaccination therapy. METHODS: In this study, we analyzed more than 17,000 primary prostate cancer tissues with a mutation-specific antibody for the IDH1R132H mutation. RESULTS: IDH1 mutation-specific staining was found in 42 of 15,531 (0...
February 9, 2018: World Journal of Urology
https://www.readbyqxmd.com/read/29425284/chromosomal-instability-in-women-with-primary-ovarian-insufficiency
#12
Sunita Katari, Mahmoud Aarabi, Angela Kintigh, Susan Mann, Svetlana A Yatsenko, Joseph S Sanfilippo, Anthony J Zeleznik, Aleksandar Rajkovic
STUDY QUESTION: What is the prevalence of somatic chromosomal instability among women with idiopathic primary ovarian insufficiency (POI)? SUMMARY ANSWER: A subset of women with idiopathic POI may have functional impairment in DNA repair leading to chromosomal instability in their soma. WHAT IS KNOWN ALREADY: The formation and repair of DNA double-strand breaks during meiotic recombination are fundamental processes of gametogenesis. Oocytes with compromised DNA integrity are susceptible to apoptosis which could trigger premature ovarian aging and accelerated wastage of the human follicle reserve...
February 7, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29423096/validation-of-a-hypoxia-related-gene-signature-in-multiple-soft-tissue-sarcoma-cohorts
#13
Lingjian Yang, Laura Forker, Joely J Irlam, Nischalan Pillay, Ananya Choudhury, Catharine M L West
Purpose: There is a need for adjuvant/neo-adjuvant treatment strategies to prevent metastatic relapse in soft tissue sarcoma (STS). Tumor hypoxia is associated with a high-risk of metastasis and is potentially targetable. This study aimed to derive and validate a hypoxia mRNA signature for STS for future biomarker-driven trials of hypoxia targeted therapy. Materials and Methods: RNA sequencing was used to identify seed genes induced by hypoxia in seven STS cell lines...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416665/baicalin-hydrate-inhibits-cancer-progression-in-nasopharyngeal-carcinoma-by-affecting-genome-instability-and-splicing
#14
Weiwei Lai, Jiantao Jia, Bin Yan, Yiqun Jiang, Ying Shi, Ling Chen, Chao Mao, Xiaoli Liu, Haosheng Tang, Menghui Gao, Ya Cao, Shuang Liu, Yongguang Tao
Baicalin hydrate (BH), a natural compound, has been investigated for many years because of its traditional medicinal properties. However, the anti-tumor activities of BH and its epigenetic role in NPC have not been elucidated. In this study, we identified that BH inhibits NPC cell growth in vivo and in vitro by inducing apoptosis and cell cycle arrest. BH epigenetically regulated genome instability by up-regulating the expression of satellite 2 (Sat2), alpha satellite (α-Sat), and major satellite (Major-Sat)...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415883/temporal-dna-pk-activation-drives-genomic-instability-and-therapy-resistance-in-glioma-stem-cells
#15
Yanling Wang, Haineng Xu, Tianrun Liu, Menggui Huang, Param-Puneet Butter, Chunsheng Li, Lin Zhang, Gary D Kao, Yanqing Gong, Amit Maity, Constantinos Koumenis, Yi Fan
Cancer stem cells (CSCs) - known to be resistant to genotoxic radiation and chemotherapy - are fundamental to therapy failure and cancer relapse. Here, we reveal that glioma CSCs are hypersensitive to radiation, but a temporal DNA repair mechanism converts the intrinsic sensitivity to genomic instability and treatment resistance. Transcriptome analysis identifies DNA-dependent protein kinase (DNA-PK) as a predominant DNA repair enzyme in CSCs. Notably, DNA-PK activity is suppressed after irradiation when ROS induce the dissociation of DNA-PKcs with Ku70/80, resulting in delayed DNA repair and radiosensitivity; subsequently, after ROS clearance, the accumulated DNA damage and robust activation of DNA-PK induce genomic instability, facilitated by Rad50-mediated cell-cycle arrest, leading to enhanced malignancy, CSC overgrowth, and radioresistance...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29415479/telomere-length-dynamics-and-the-evolution-of-cancer-genome-architecture
#16
REVIEW
Kez Cleal, Kevin Norris, Duncan Baird
Telomeres are progressively eroded during repeated rounds of cell division due to the end replication problem but also undergo additional more substantial stochastic shortening events. In most cases, shortened telomeres induce a cell-cycle arrest or trigger apoptosis, although for those cells that bypass such signals during tumour progression, a critical length threshold is reached at which telomere dysfunction may ensue. Dysfunction of the telomere nucleoprotein complex can expose free chromosome ends to the DNA double-strand break (DSB) repair machinery, leading to telomere fusion with both telomeric and non-telomeric loci...
February 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29413990/mitochondrial-gene-expression-changes-in-cultured-human-skin-cells-following-simulated-sunlight-irradiation
#17
J Kelly, J E Murphy
BACKGROUND: Exposure of skin to simulated sunlight irradiation (SSI) has being extensively researched and shown to be the main cause for changes in the skin including changes in cellular function and generation of reactive oxygen species (ROS). This oxidative stress can subsequently exert downstream effects and the subcellular compartments most affected by this oxidative stress are mitochondria. The importance of functional mitochondrial morphology is apparent as morphological defects are related to many human diseases including diabetes mellitus, liver disease, neurodegenerative diseases, aging and cancer...
November 10, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29413422/prc1-linking-cytokinesis-chromosomal-instability-and-cancer-evolution
#18
REVIEW
Jing Li, Marlene Dallmayer, Thomas Kirchner, Julian Musa, Thomas G P Grünewald
Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29412049/ion-channels-in-cancer-are-cancer-hallmarks-oncochannelopathies
#19
Natalia Prevarskaya, Roman Skryma, Yaroslav Shuba
Genomic instability is a primary cause and fundamental feature of human cancer. However, all cancer cell genotypes generally translate into several common pathophysiological features, often referred to as cancer hallmarks. Although nowadays the catalog of cancer hallmarks is quite broad, the most common and obvious of them are 1) uncontrolled proliferation, 2) resistance to programmed cell death (apoptosis), 3) tissue invasion and metastasis, and 4) sustained angiogenesis. Among the genes affected by cancer, those encoding ion channels are present...
April 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29404399/the-turtle-and-the-rabbit-story-in-a-modern-pi3-key
#20
Miriam Martini, Maria Chiara De Santis, Emilio Hirsch
Mitosis is a complex process controlling proper distribution of chromosomes and preventing genomic instability, a typical hallmark of cancer. We recently reported that that a class II isoform of Phosphoinositide 3-kinase (PI3K), PI3K-C2α, is involved in the organization of the mitotic spindle. Our study demonstrate that, differently to all other PI3K isoforms, PI3K-C2α shows an unexpected tumor suppressor function independent of its catalytic activity.
2018: Molecular & Cellular Oncology
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