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      Effect of systemic treatment on the micronuclei frequency in the peripheral blood of patients with metastatic colorectal cancer

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          Abstract

          Colorectal cancer (CRC) is the third most diagnosed type of cancer affecting males, and the second most diagnosed type of cancer affecting females, and one of the leading causes of cancer-related mortality globally. The estimation of the micronuclei (MN) frequency in peripheral blood lymphocytes (PBLs) from patients with CRC is proposed as a prognostic/predictive easy-to-use biomarker. In this study, we aimed to investigate the effects of systemic treatment on the MN frequency in PBLs from patients with CRC in order to determine the effectiveness of the MN frequency as a biomarker. For this purpose, from 2016 to 2018, we quantified the MN frequency as a prognostic/predictive biomarker in serial samples from 25 patients with metastatic CRC (mCRC) using cytokinesis block micronucleus assay (CBMN assay). The MN frequency in the PBLs of the patients was evaluated before, during the middle and at the end of the therapy (approximately 0, 3 and 6 months). The results revealed a common pattern regarding the fluctuation in the MN frequency. Statistical analysis confirmed that when the disease response was estimated with radiological criteria, a good response was depicted at the MN frequency and vice versa. Consequently, the findings of this study suggest that the MN frequency may serve as a promising prognostic/predictive biomarker for the monitoring of the treatment response of patients with CRC.

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          Most cited references28

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          Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors.

          In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.
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            Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells.

            Micronuclei (MN) and other nuclear anomalies such as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) are biomarkers of genotoxic events and chromosomal instability. These genome damage events can be measured simultaneously in the cytokinesis-block micronucleus cytome (CBMNcyt) assay. The molecular mechanisms leading to these events have been investigated over the past two decades using molecular probes and genetically engineered cells. In this brief review, we summarise the wealth of knowledge currently available that best explains the formation of these important nuclear anomalies that are commonly seen in cancer and are indicative of genome damage events that could increase the risk of developmental and degenerative diseases. MN can originate during anaphase from lagging acentric chromosome or chromatid fragments caused by misrepair of DNA breaks or unrepaired DNA breaks. Malsegregation of whole chromosomes at anaphase may also lead to MN formation as a result of hypomethylation of repeat sequences in centromeric and pericentromeric DNA, defects in kinetochore proteins or assembly, dysfunctional spindle and defective anaphase checkpoint genes. NPB originate from dicentric chromosomes, which may occur due to misrepair of DNA breaks, telomere end fusions, and could also be observed when defective separation of sister chromatids at anaphase occurs due to failure of decatenation. NBUD represent the process of elimination of amplified DNA, DNA repair complexes and possibly excess chromosomes from aneuploid cells.
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              The micronucleus test.

              W. Schmid (1975)
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                March 2019
                07 January 2019
                07 January 2019
                : 17
                : 3
                : 2703-2712
                Affiliations
                [1 ]Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Greece
                [2 ]Laboratory of Toxicology, Medical School, University of Crete, 71409 Heraklion, Greece
                [3 ]Department of Forensic Sciences and Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece
                [4 ]Laboratory of Anatomy and Histology, Nursing School, National and Kapodistrian University of Athens, 11527 Athens, Greece
                [5 ]Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece
                [6 ]Department of Medical Oncology, University General Hospital of Heraklion, 71110 Heraklion, Greece
                Author notes
                Correspondence to: Dr John Tsiaoussis, Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, Voutes, 71110 Heraklion, Greece, E-mail: tsiaoussis@ 123456uoc.gr
                Professor Aristidis Tsatsakis, Department of Forensic Sciences and Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece, E-mail: tsatsaka@ 123456uoc.gr
                Article
                OL-0-0-9895
                10.3892/ol.2019.9895
                6365930
                30854044
                ea065a5d-ef38-46fc-b44b-f81f96373f64
                Copyright: © Nikolouzakis et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 02 November 2018
                : 12 December 2018
                Categories
                Articles

                Oncology & Radiotherapy
                metastatic colorectal cancer,micronucleus,prognostic biomarker,predictive biomarker,micronuclei frequency,cytokinesis block micronucleus assay

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