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https://www.readbyqxmd.com/read/29727725/dna-damage-and-tissue-repair-what-we-can-learn-from-planaria
#1
REVIEW
Paul G Barghouth, Manish Thiruvalluvan, Melanie LeGro, Néstor J Oviedo
Faithful renewal of aging and damaged tissues is central to organismal lifespan. Stem cells (SCs) generate the cellular progeny that replenish adult tissues across the body but this task becomes increasingly compromised over time. The age related decline in SC-mediated tissue maintenance is a multifactorial event that commonly affects genome integrity. The presence of DNA damage in SCs that are under continuous demand to divide poses a great risk for age-related disorders such as cancer. However, performing analysis of SCs with genomic instability and the DNA damage response during tissue renewal present significant challenges...
May 3, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29721644/morphology-oriented-epigenetic-research
#2
REVIEW
Sohei Kitazawa, Ryuma Haraguchi, Riko Kitazawa
Cytosine methylation plays a major role in the regulation of sequential and tissue-specific expression of genes. De novo aberrant DNA methylation and demethylation are also crucial processes in tumorigenesis and tumor progression. The mechanisms of how and when such aberrant methylation and demethylation occur in tumor cells are still obscure, however. To evaluate subtle epigenetic alteration among minor subclonal populations, morphology-oriented epigenetic analysis is requisite, especially where heterogeneity and flexibility are as notable as in the process of cancer progression and cellular differentiation at critical stages...
May 2, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29697303/2017-michael-fry-award-lecture-when-dna-is-actually-not-a-target-radiation-epigenetics-as-a-tool-to-understand-and-control-cellular-response-to-ionizing-radiation
#3
Igor Koturbash
In addition to the generally accepted potential of ionizing radiation to cause DNA damage, its capability to target the cellular epigenome has become increasingly evident. Epigenetics unifies the chemical marks and molecules that collectively facilitate the proper reading of genetic material. Among the epigenetic mechanisms of regulation, methylation of DNA is known to be the key player in the postirradiation response by controlling the expression of genetic information and activity of transposable elements...
April 26, 2018: Radiation Research
https://www.readbyqxmd.com/read/29677173/what-does-this-mutation-mean-the-tools-and-pitfalls-of-variant-interpretation-in-lymphoid-malignancies
#4
REVIEW
Yann Guillermin, Jonathan Lopez, Kaddour Chabane, Sandrine Hayette, Claire Bardel, Gilles Salles, Pierre Sujobert, Sarah Huet
High throughput sequencing (HTS) is increasingly important in determining cancer diagnoses, with subsequent prognostic and therapeutic implications. The biology of cancer is becoming increasingly deciphered and it is clear that therapy needs to be individually tailored. Whilst translational research plays an important role in lymphoid malignancies, few guidelines exist to guide biologists and routine laboratories through this constantly evolving field. In this article, we review the challenges of interpreting HTS in lymphoid malignancies and provide a toolkit to interpret single nucleotide variants obtained from HTS...
April 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29348271/intratumoral-payload-concentration-correlates-with-the-activity-of-antibody-drug-conjugates
#5
Donglu Zhang, Shang-Fan Yu, S Cyrus Khojasteh, Yong Ma, Thomas H Pillow, Jack D Sadowsky, Dian Su, Katherine R Kozak, Keyang Xu, Andrew G Polson, Peter Dragovich, Cornelis Eca Hop
Antibody-drug conjugates (ADCs) have become important scaffolds for targeted cancer therapies. However, ADC exposure - response correlation is not well characterized. We demonstrated that intratumor payload exposures correlated well with the corresponding efficacies of several disulfide-linked ADCs bearing an DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2-expressing xenograft models. The correlation suggests that a threshold concentration of intratumor payload is required to support sustained efficacy and an ADC can deliver an excessive level of payload to tumors that does not enhance efficacy ('Plateau' effect)...
January 18, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29274896/impact-of-oxidative-stress-on-telomere-biology
#6
REVIEW
Wareed Ahmed, Joachim Lingner
Telomere integrity is essential for genome stability and it regulates cell proliferation and tissue renewal. Several lines of evidence indicate that telomeres are particularly sensitive to oxidative damage. Moreover, recent studies demonstrate striking inhibitory effects of oxidative damage on telomerase activity. On the other hand, several mechanisms have been uncovered that either counteract oxidative damage at telomeres or remove the modified lesions. Here, we review the current understanding of oxidative damage and protection of telomeric DNA...
January 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29247855/-omics-in-oral-cancer-new-approaches-for-biomarker-discovery
#7
REVIEW
Vertika Rai, Rashmi Mukherjee, Ananta K Ghosh, Aurobinda Routray, Chandan Chakraborty
OBJECTIVES: In this review paper, we explored the application of "omics" approaches in the study of oral cancer (OC). It will provide a better understanding of how "omics" approaches may lead to novel biomarker molecules or molecular signatures with potential value in clinical practice. A future direction of "omics"-driven research in OC is also discussed. METHODS: Studies on "omics"-based approaches [genomics/proteomics/transcriptomics/metabolomics] were investigated for differentiating oral squamous cell carcinoma,oral sub-mucous fibrosis, oral leukoplakia, oral lichen planus, oral erythroplakia from normal cases...
March 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29204834/oesophageal-stem-cells-and-cancer
#8
Maria P Alcolea
Oesophageal cancer remains one of the least explored malignancies. However, in recent years its increasing incidence and poor prognosis have stimulated interest from the cancer community to understand the pathways to the initiation and progression of the disease.Critical understanding of the molecular processes controlling changes in stem cell fate and the cross-talk with their adjacent stromal neighbours will provide essential knowledge on the mechanisms that go awry in oesophageal carcinogenesis. Advances in lineage tracing techniques have represented a powerful tool to start understanding changes in oesophageal cell behaviour in response to mutations and mutagens that favour tumour development...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29197683/long-range-telomere-regulation-of-gene-expression-telomere-looping-and-telomere-position-effect-over-long-distances-tpe-old
#9
Wanil Kim, Jerry W Shay
The human cellular reverse transcriptase, telomerase, is very tightly regulated in large long-lived species. Telomerase is expressed during early human fetal development, is turned off in most adult tissues, and then becomes reactivated in almost all human cancers. However, the exact mechanism regulating these switches in expression are not known. We recently described a phenomenon where genes are regulated by telomere length dependent loops (telomere position effects over long distances; TPE-OLD). The hTERT gene is ~ 1...
January 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29164055/micrornas-and-acute-myeloid-leukemia-chemoresistance-a-mechanistic-overview
#10
REVIEW
Martino Marco Gabra, Leonardo Salmena
Up until the early 2000s, a functional role for microRNAs (miRNAs) was yet to be elucidated. With the advent of increasingly high-throughput and precise RNA-sequencing techniques within the last two decades, it has become well established that miRNAs can regulate almost all cellular processes through their ability to post-transcriptionally regulate a majority of protein-coding genes and countless other non-coding genes. In cancer, miRNAs have been demonstrated to play critical roles by modifying or controlling all major hallmarks including cell division, self-renewal, invasion, and DNA damage among others...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29157078/evolving-paradigms-for-the-biological-response-to-low-dose-ionizing-radiation-the-role-of-epigenetics
#11
Paul N Schofield, Monika Kondratowicz
PURPOSE: In the late 1990s, it had become clear that the long-standing paradigm for the action of radiation on living cells and organisms did not have sufficient power to explain the observed effects of low dose ionizing radiation. The purpose of this commentary is to examine the experiments that lead up to the modification of the classic paradigm consequent on these observations, their historical precedents, and the development of our understanding of the role of epigenetics in low dose radiation effects...
December 1, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28993779/natural-killer-cell-response-to-chemotherapy-stressed-cancer-cells-role-in-tumor-immunosurveillance
#12
REVIEW
Alessandra Zingoni, Cinzia Fionda, Cristiana Borrelli, Marco Cippitelli, Angela Santoni, Alessandra Soriani
Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28969871/alternative-lengthening-of-telomeres-dna-repair-pathways-converge
#13
REVIEW
Alexander P Sobinoff, Hilda A Pickett
Telomeres shorten during each cellular division, with cumulative attrition resulting in telomeric damage and replicative senescence. Bypass of replicative senescence precipitates catastrophic telomere shortening or crisis, and is characterized by widespread genomic instability. Activation of a telomere maintenance mechanism (TMM) is necessary to stabilise the genome and establish cellular immortality through the reconstitution of telomere capping function. The alternative lengthening of telomeres (ALT) pathway is a TMM frequently activated in tumors of mesenchymal or neuroepithelial origin...
December 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28966990/a-crispr-view-of-gene-regulation
#14
Budhaditya Banerjee, Richard I Sherwood
Due to plummeting costs, whole genome sequencing of patients and cancers will soon become routine medical practice; however, we cannot currently predict how non-coding genotype affects cellular gene expression. Gene regulation research has recently been dominated by observational approaches that correlate chromatin state with regulatory function. These approaches are limited to the available genotypes and cannot scratch the surface of possible sequence combinations, and thus there is a need for perturbation-based approaches to better understand how DNA encodes gene regulatory functions...
February 2017: Current Opinion in Systems Biology
https://www.readbyqxmd.com/read/28947971/dynamic-circulating-tumor-dna-quantificaton-for-the-individualization-of-non-small-cell-lung-cancer-patients-treatment
#15
Mariano Provencio, María Torrente, Virgina Calvo, Lourdes Gutiérrez, David Pérez-Callejo, Clara Pérez-Barrios, Miguel Barquín, Ana Royuela, Begoña Rodriguez-Alfonso, Miguel Sotelo, Juan Luis Cruz-Bermúdez, Miriam Mendez, Alberto Cruz-Bermúdez, Atocha Romero
BACKGROUND: Liquid biopsy has evolved from being a promising line to becoming a validated approach for biomarker testing. However, its utility for individualization of therapy has been scarcely reported. In this study, we show how monitoring levels of EGFR mutation in plasma can be useful for the individualization of treatment. RESULTS: Longitudinal EGFR mutation levels in plasma always correlated with tumor response ascertained by RECIST criteria. Moreover, decreasing EGFR mutation levels were detected in all patients benefiting from locoregional radiotherapy, whereas the opposite occurred when a patient progressed soon after radiotherapy treatment...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28927527/dna-mismatch-repair-and-its-many-roles-in-eukaryotic-cells
#16
REVIEW
Dekang Liu, Guido Keijzers, Lene Juel Rasmussen
DNA mismatch repair (MMR) is an important DNA repair pathway that plays critical roles in DNA replication fidelity, mutation avoidance and genome stability, all of which contribute significantly to the viability of cells and organisms. MMR is widely-used as a diagnostic biomarker for human cancers in the clinic, and as a biomarker of cancer susceptibility in animal model systems. Prokaryotic MMR is well-characterized at the molecular and mechanistic level; however, MMR is considerably more complex in eukaryotic cells than in prokaryotic cells, and in recent years, it has become evident that MMR plays novel roles in eukaryotic cells, several of which are not yet well-defined or understood...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28798901/translational-dysregulation-in-cancer-molecular-insights-and-potential-clinical-applications-in-biomarker-development
#17
REVIEW
Christos Vaklavas, Scott W Blume, William E Grizzle
Although transcript levels have been traditionally used as a surrogate measure of gene expression, it is increasingly recognized that the latter is extensively and dynamically modulated at the level of translation (messenger RNA to protein). Over the recent years, significant progress has been made in dissecting the complex posttranscriptional mechanisms that regulate gene expression. This advancement in knowledge came hand in hand with the progress made in the methodologies to study translation both at gene-specific as well as global genomic level...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28757314/using-ion-torrent-sequencing-to-study-genetic-mutation-profiles-of-fatal-thyroid-cancers
#18
Jin-Ying Lu, Wern-Cherng Cheng, Kuen-Yuan Chen, Chia-Chi Lin, Ching-Chung Chang, Kuan-Ting Kuo, Pei-Lung Chen
BACKGROUND/PURPOSE: Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumor's genetic information. METHODS: We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes...
July 27, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28738540/regulatory-players-of-dna-damage-repair-mechanisms-role-in-cancer-chemoresistance
#19
REVIEW
Kunnathur Murugesan Sakthivel, Sreedharan Hariharan
DNA damaging agents are most common in chemotherapeutic molecules that act against cancer. However, cancer cells possess inherent biological features to overcome DNA damages by activating various distinct repair mechanisms and pathways. Importantly, various oncogenes, cancer stem cells (CSCs), hypoxic environment, transcription factors and bystander signaling that are activated in the cancer cells influence DNA repair, thereby effectively repairing the DNA damage. Repaired cancer cells often become more resistance to further therapy and results in disease recurrence...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28738408/cgas-surveillance-of-micronuclei-links-genome-instability-to-innate-immunity
#20
Karen J Mackenzie, Paula Carroll, Carol-Anne Martin, Olga Murina, Adeline Fluteau, Daniel J Simpson, Nelly Olova, Hannah Sutcliffe, Jacqueline K Rainger, Andrea Leitch, Ruby T Osborn, Ann P Wheeler, Marcin Nowotny, Nick Gilbert, Tamir Chandra, Martin A M Reijns, Andrew P Jackson
DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane...
August 24, 2017: Nature
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