1.Mutagenic effects of Fuji-One and monitor in mice
Journal of Practical Medicine 2002;435(11):23-27
Nowdays in Vietnam, Fuji-One and Monitor are organophosphorus pesticides widely used in agriculture. In order to investigate chromosomal mutagenic effects of Fuji-One and Monitor, we have carried out this study in mice. 4 group of mice were analyzed: Negative control group: 16 male mice were non-exposed to pesticides. Positive control group: 15 male mice were injected into the peritoneum with cyclophosphamide, which is a kind of mutagen. Fuji-One group: 5 male mice were injected into the peritoneum with Monitor. Analyzing of frequencies of chromosomal aberration in bone marrow cells and testicular cells of mice, we found that: (1) Monitor can cause chromosomal mutagenic effects in the bone marrow cells. (2) Fuji-One can cause chromosomal structural and numerical aberration. (3) The rate of chromosomal aberration in Fuji-One group was lower than those in positive control group but they were higher than those in monitor group
Mutagenesis
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Chromosomal Instability
2.Classification of Colorectal Cancer Based on Clinical, Morphological and Molecular Features.
Journal of the Korean Society of Coloproctology 2008;24(6):497-504
Colorectal cancer (CRC) has been assumed for many years to be a homogenous condition with the vast majority developing within preexisting-adenomas. However, over the last two-decades, it has become clear that CRC evolves through multiple pathways at the genetic and the epigenetic level. Each of these processes is associated with a unique genetic or epigenetic signature identifiable in the tumor cells. The pathway may be defined on the basis of three molecular features: 1) chromosomal instability (CIN), 2) microsatellite instability (MSI), and 3) CpG island methylator phenotype (CIMP). Those molecular pathways are determined at an early evolutionary stage and are fully established within early cancer. Recently, five subgroups were outlined by using morphological findings and associated molecular changes: type 1 (CIN-stable/ MSI-H/CIMP-H), type 2 (CIN-stable/MSI-L or MSS/ CIMP-H), type 3 (CIN-unstable/MSI-L or MSS/CIMP-L), type 4 (CIN-instable/MSS/CIMP-neg), and type 5 (CIN- stable/MSI-H/CIMP-neg). This approach to the classification of CRC should accelerate understanding of causation and will have an impact on clinical management in the areas of both prevention and treatment.
Chromosomal Instability
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Colorectal Neoplasms
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CpG Islands
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Epigenomics
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Microsatellite Instability
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Phenotype
3.Highly expressed protein in cancer (Hec 1) and chromosome instability.
Acta Academiae Medicinae Sinicae 2007;29(1):137-142
Highly expressed in cancer (Hec 1), locating at centromere during cell mitosis, plays an important role in the pathway of spindle checkpoint. Hec 1-Nuf 2 complex is the structural basis for the recruitment of Mad 1/Mad 2 complex of spindle checkpoint. Hec 1 can interact with the subunit of 26S proteasome and inhibit the degradation of cyclins. It was initially identified as a protein interacting with Rb by yeast two-hybridization assay. Rb interacts with Hec 1 to regulate the binding ability of Smc 1 with DNA and participates in the regulation of M phase. Hec 1 mainly expresses at G2/M phase and functions through the phosphorylation by kinase Nek 2. Hec 1 is over expressed in some cancer cell lines and amplified in tumor tissues. The dysfunction of Hec 1 gene may cause severe impediment of chromosome separation and finally lead to chromosome instability, which is closely associated with the occurrence and development of tumors. Therefore, Hec 1 may become a new target of tumor gene therapy.
Chromosomal Instability
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Humans
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Neoplasms
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genetics
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Nuclear Proteins
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genetics
4.Isolation of a Variant Strain of Pleurotus eryngii and the Development of Specific DNA Markers to Identify the Variant Strain.
Hyun Jun LEE ; Sang Woo KIM ; Jae San RYU ; Chang Yun LEE ; Hyeon Su RO
Mycobiology 2014;42(1):46-51
A degenerated strain of Pleurotus eryngii KNR2312 was isolated from a commercial farm. Random amplified polymorphic DNA analysis performed on the genomic DNA of the normal and degenerated strains of this species revealed differences in the DNA banding pattern. A unique DNA fragment (1.7 kbp), which appeared only in the degenerated strain, was isolated and sequenced. Comparing this sequence with the KNR2312 genomic sequence showed that the sequence of the degenerated strain comprised three DNA regions that originated from nine distinct scaffolds of the genomic sequence, suggesting that chromosome-level changes had occurred in the degenerated strain. Using the unique sequence, three sets of PCR primers were designed that targeted the full length, the 5' half, and the 3' half of the DNA. The primer sets P2-1 and P2-2 yielded 1.76 and 0.97 kbp PCR products, respectively, only in the case of the degenerated strain, whereas P2-3 generated a 0.8 kbp product in both the normal and the degenerated strains because its target region was intact in the normal strain as well. In the case of the P2-1 and P2-2 sets, the priming regions of the forward and reverse primers were located at distinct genomic scaffolds in the normal strain. These two primer sets specifically detected the degenerate strain of KNR2312 isolated from various mushrooms including 10 different strains of P. eryngii, four strains of P. ostreatus, and 11 other wild mushrooms.
Agaricales
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Chromosomal Instability
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DNA*
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Genetic Markers*
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Pleurotus*
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Polymerase Chain Reaction
5.Relationship between CpG island methylator phenotype and genetic instability in sporadic colorectal cancer.
Guo-Xiang CAI ; Ye XU ; San-Jun CAI ; Ying-Qiang SHI ; Peng LIAN ; Jun-Jie PENG ; Zu-Qing GUAN ; Xiang DU
Chinese Journal of Gastrointestinal Surgery 2007;10(6):555-560
OBJECTIVETo explore the relationship between CpG island methylator phenotype(CIMP) and genetic instability in sporadic colorectal cancer(SCRC).
METHODSSeventy-one SCRC patients were enrolled in this study. Promotor methylation status of five genes including P14(ARF ), hMLH1, P16(INK4a), MGMT and MINT1 was detected with methylation specific PCR to confirm CIMP. Microsatellite instability (MSI) status was evaluated with two microsatellite loci of BAT25 and BAT26, and the ploidy was detected with flow cytometry. The association between CIMP and MSI as well as chromosomal instability(CIN) was examined.
RESULTSThe positive rates of CIMP, MSI and aneuploidy were 21.1% (15/71), 9.9% (7/71) and 73.5% (50/68) respectively. The positive rate of MSI in positive CIMP patients was higher than that in negative CIMP ones, but the difference was not significant (20.0% vs 7.1%,P=0.158). The positive rate of MSI was 57.1% in patients with hMLH1 gene promotor hypermethylation, which was significantly higher than that (4.7%) in patients without hMLH1 gene promotor hypermethylation (P=0.001). SCRCs with positive CIMP displayed significant inclination of diploidy (P=0.003). The positive rate of diploidy among SCRCs with CIMP was 61.5% while only 18.2% of cases without CIMP demonstrated diploid.
CONCLUSIONSSCRCs with positive CIMP are significantly more likely to be diploid. Simultaneous multiple genes hypermethylation represented by CIMP may be an epigenetic mechanism competing with the genetic mechanism of CIN.
Chromosomal Instability ; Colorectal Neoplasms ; genetics ; CpG Islands ; DNA Methylation ; Genome, Human ; Humans ; Microsatellite Instability ; Phenotype
6.Genomic Instability in Colorectal Cancer; from Bench to Bed.
Journal of the Korean Society of Coloproctology 2009;25(2):129-138
Colorectal cancer is a disease developed by the accumulation of genomic alteration. Two genomic instability pathways, chromosomal instability pathway and microsatellite instability pathway, are known as the main pathways of the development of colorectal cancer. These are almost always mutually exclusive and tumors developed through each pathways show distinct clinicopathologic features. For the reason, molecular markers which represent each genomic instability pathways have been a candidate for translational research to find out prognostic or predictive factors. Loss of heterozygosity and aneuploidy are the hallmark of chromosomal instability and regarded as poor prognostic markers, whereas tumors with high frequency of microsatellite instability show better prognosis than microsatellite stable tumor. As a predictive factor of response from chemotherapy, loss of heterozygosity seems to be associated with a survival benefit from 5-FU adjuvant therapy. MSI-H has been reported as a predictive factor for poor response to 5-FU adjuvant chemotherapy. However, these molecular markers are not accepted to use in the clinic yet, since some of this kind of studies reported contradictory results. Further study will be needed to make more concrete evidences for these markers and to identify new molecular markers for routine use in the clinic.
Aneuploidy
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Chemotherapy, Adjuvant
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Chromosomal Instability
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Colorectal Neoplasms
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Fluorouracil
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Genomic Instability
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Loss of Heterozygosity
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Microsatellite Instability
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Microsatellite Repeats
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Prognosis
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Translational Medical Research
7.Clinical Application of Genetics in Management of Colorectal Cancer.
Intestinal Research 2014;12(3):184-193
The extensive study of genetic alterations in colorectal cancer (CRC) has led to molecular diagnostics playing an increasingly important role in CRC diagnosis and treatment. Currently, it is believed that CRC is a consequence of the accumulation of both genetic and epigenetic genomic alterations. It is known that there are at least 3 major pathways that lead to colorectal carcinogenesis: (1) the chromosomal instability pathway, (2) the microsatellite instability pathway, and (3) the cytosine-phospho-guanine island methylator phenotype pathway. With recent advances in CRC genetics, the identification of specific molecular alterations responsible for CRC pathogenesis has directly influences clinical care. Patients at high risk for developing CRC can be identified by genetic testing for specific molecular alterations, and the use of molecular biomarkers for predictive and prognostic purposes is also increasing. This is clearly supported by the recent advances in genetic testing for CRC whereby specific molecular alterations are identified for the purpose of guiding treatment with targeting therapies such as anti-endothelial growth factor receptor monoclonal antibodies.
Antibodies, Monoclonal
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Biomarkers
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Carcinogenesis
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Chromosomal Instability
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Colorectal Neoplasms*
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Diagnosis
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Epigenomics
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Genetic Testing
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Genetics*
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Humans
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Microsatellite Instability
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Pathology, Molecular
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Phenotype
8.Chromosomal Instability in the Peripheral Blood Lymphocytes of an Ovarian Cancer Patient Undergoing Chemotherapy.
Se Jin OH ; Hye Sung MOON ; Jungwon HUH
Laboratory Medicine Online 2012;2(4):223-225
Chemotherapy agents can induce chromosomal instability, including a variety of chromatid or chromosomal aberrations. However, only limited data is available on the effect of chemotherapy on the kinetics of chromosomal instability in peripheral blood lymphocytes. Here, we report the case of an ovarian cancer patient who showed chromosomal instability in peripheral blood lymphocytes while undergoing chemotherapy. Karyotypic analysis of peripheral blood 1 day after administration of cisplatin and etoposide showed chromosomal or chromatid aberrations, including gaps, breaks, and fragmentation. Chromosome study after completion of the first chemotherapy cycle showed normal karyotype. This finding suggests that chemotherapeutic agents can induce transient chromosomal instability in peripheral blood lymphocytes.
Chromatids
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Chromosomal Instability
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Chromosome Aberrations
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Cisplatin
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Etoposide
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Humans
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Karyotype
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Kinetics
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Lymphocytes
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Ovarian Neoplasms
9.Clinical and Pathological Significance of the Genetic Analysis in Colorectal Carcinomas.
The Korean Journal of Gastroenterology 2004;43(5):275-282
The molecular genetics of colorectal carcinomas are among the best understood of common human cancers. Three inter-related molecular pathways are involved. The chromosomal instability pathway begins with inactivation of the APC/beta-catenin genes followed by activation of oncogenes and inactivation of additional suppressor genes, commonly with high frequency of allelic losses, cytogenetic abnormalities. The microsatellite instability pathway begins with inactivating one of a group of genes responsible for DNA nucleotide mismatch repair leading to extensive mutations in both repetitive and non-repetitive DNA sequences with low frequencies of allelic losses and rare alteration of tumor DNA content. Finally, the CpG island methylation pathway involves inactivation of genes by methylation of cytosines in promoter regions to silence gene expression without DNA sequence alterations. Molecular genetics have the potential for clinical applications. Combination of genetic classification of high levels of microsatellite instability (MSI-H), gene expression analysis of mismatch repair genes and subsequent mutation analysis of inactivated genes can be used as an effective method for the identification of hereditary nonpolyposis colorectal carcinoma patients. Molecular genetic alterations have been proposed to be of prognostic value, including allelic deletion on chromosome 18q, and on chromosome 17p. MSI-H has been reported as a marker for better prognosis. Individualizing chemoradiation by use of predictive markers for response or resistance to therapy is important in patients with advanced disease or candidacy for adjuvant therapy.
Chromosomal Instability
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Colorectal Neoplasms/diagnosis/*genetics/pathology
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English Abstract
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Humans
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Microsatellite Repeats
10.Sister Chromatid Exchange Frequencies in Stomach Cancer Patients.
Chan Sang PARK ; Dae Kwang KIM
Korean Journal of Anatomy 1999;32(5):615-617
This study was made to show the effect of stomach cancer on chromosome by sister chromatid exchange (SCE) analysis, because very few studies have reported. Metaphase preparation from peripheral blood lymphocytes of 12 patients were harvested before operation, along with those of 10 healthy control subjects. Mean SCE frequency in the stomach cancer patients was 7.0107+/-1.5720 as compared with 5.8267+/-0.7646 in controls. SCE values of patients with stomach cancer were significantly higher than those of control (p<0.035). This results suggest that patients with stomach cancer show a degree of chromosomal instability that might be related to a predisposition to neoplasia.
Chromosomal Instability
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Humans
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Lymphocytes
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Metaphase
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Siblings*
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Sister Chromatid Exchange*
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Stomach Neoplasms*
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Stomach*