• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2847-2850
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• 2014

Background: Retinoblastoma is a rare malignant intraocular neoplasm. About 90% of cases feature a germline mutation in the RB1 gene and these will develop retinoblastoma during their early childhood. An association between mutations in germline cells and aging has been demonstrated. This suggests a higher incidence of childhood cancer including retinoblastoma among children of older parents. Materials and Methods: In the present study we aimed to determine the association of paternal and maternal age with an increased risk of retinoblastoma in a case-control study in Iranian population. The study was carried out on 240 persons who were born during 1984-2012 in Mahak and Mofid hospitals in Tehran, Iran. The statistical analysis included studying the mean age of parents and in order to know whether parental age of patients is different from parental age of control group, (t-test) compare averages test is used perfectly. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The results of statistical analysis including the study of mean parental age by the use of (t-test) compare averages test showed a significant difference between parental ages of patients and controls. Logistic regression showed that coefficients were significant for maternal but not paternal age. Conclusions: Our findings indicate that advanced maternal age can increase the risk of retinoblastoma in offspring, but the paternal age has no significant effect.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8177-8186
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• 2016

The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta ($pol{\beta}{\Delta}_{208-304}$) specific for ovarian cancer. $Pol{\beta}{\Delta}_{208-304}$ has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. $Pol{\beta}{\Delta}_{208-304}$ cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards $H_2O_2$ and UV when compared with HeLa cells alone. It has been shown that cell death in $Pol{\beta}{\Delta}_{208-304}$ transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

• BMB Reports
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• v.51 no.10
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• pp.481-483
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• 2018

Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

• The Journal of the Korean bone and joint tumor society
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• v.8 no.3
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• pp.69-75
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• 2002

Werner's syndrome is a rare autosomal recessive disorder manifesting as premature aging. It is also known to be characterized by a high frequency of malignant tumors, especially sarcomas. However, Werner's syndrome may be not only a premature aging disease but also a cancer syndrome, because the malignant tumors in these patients are different from those of normal population with respect to involved site, histological type, and age of onset. Recent studies found Werner's syndrome was caused by a mutation of Werner helicase suggesting that WRN helicase may participate in metabolism and repair of DNA. And a dysfunction of WRN helicase may induce the genomic instability causing somatic mutations. Further studies of Werner's syndrome associated with sarcoma might give much informations about the normal aging process and the pathogenesis of sarcomas.

• Journal of the Korean Chemical Society
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• v.50 no.2
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• pp.116-122
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• 2006

In this study we extracted DNA from 100 tissues of breast cancer patients and 103 normals. Then we confirmed single-nucleotide polymorphism(SNP) using PCR-DHPLC(polymerase chain reaction-denaturing high performance liquid chromatogrphy).Also, we studied SNP of samples using several columns to identify relation between packing materials of column and resolution.As a result, we identified 4 C/A, C/G genotypes(4%) in exon 5 and 37 T del genotypes(37%) in exon 8 among 100 breast cancer tissues and 2 in exon 5, 9 in exon 8 among 103 normal samples.In resolution test, we confirmed that PS-DVB(poly styrene-divinylbenzen) column is more efficient than C18 column.

• Journal of Microbiology and Biotechnology
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• v.10 no.5
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• pp.620-627
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• 2000

To determine the prevalence of genetic polymorphisms in Epstein-Barr virus (EBV) strains in the Korean population, the restriction site polymorphisms for BamHI and XhoI enzymes were analyzed with 16 EBV isolates from cancer patients and 7 EBV isolates from healthy carriers, using polymerase chain reaction techniques. None of the 23 isolates were found to carry an extra BamHI site in the BamHI F-fragment (f-variant). Of the 12 type-1 isolates from the cancer patients, 10 lost both the LMP1 XhoI site and the BamHI site between the BamHi W1* and I1* fragments (a W1*I1* fusion variant or type C). The latter W1*I1* fusion variant was due to a mutation of thymidine to adenine, as evidenced by a sequence analysis. The remaining two type-1 isolates showed either no variation at both sites or the loss of only the XhoI site. In contrast, two type-2 isolates and two intertypic recombinants with a type-1 allele at the EBNA2 locus and type-2 alleles at all or some of the EBNA3 loci retained both enzyme sites. In similar analyses of the 7 isolates from the healthy carriers, five of six type-1 isolates lost these two sites, however, one type-2 isolate did not. These results clearly indicate a strong association of both the LMP1 XhoI site loss and the W1*I1* fusion variant with the type-1 rather than the type-2 EBV strains circulating in the immunocompetent Korean carriers.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.12.1-12.12
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• 2018

Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

• Journal of Pathology and Translational Medicine
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• v.52 no.6
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• pp.386-395
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• 2018

Background: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p=.003) and distant metastasis (p=.001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p<.001), but not for recurrence-free survival (p=.151). Conclusions: Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

• Genomics & Informatics
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• v.19 no.4
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• pp.46.1-46.11
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• 2021

Moringa oleifera is nowadays raising as the most preferred medicinal plant, as every part of the moringa plant has potential bioactive compounds which can be used as herbal medicines. Some bioactive compounds of M. oleifera possess potential anti-cancer properties which interact with the apoptosis protein p53 in cancer cell lines of oral squamous cell carcinoma. This research work focuses on the interaction among the selected bioactive compounds derived from M. oleifera with targeted apoptosis protein p53 from the apoptosis pathway to check whether the bioactive compound will induce apoptosis after the mutation in p53. To check the toxicity and drug-likeness of the selected bioactive compound derived from M. oleifera based on Lipinski's Rule of Five. Detailed analysis of the 3D structure of apoptosis protein p53. To analyze protein's active site by CASTp 3.0 server. Molecular docking and binding affinity were analyzed between protein p53 with selected bioactive compounds in order to find the most potential inhibitor against the target. This study shows the docking between the potential bioactive compounds with targeted apoptosis protein p53. Quercetin was the most potential bioactive compound whereas kaempferol shows poor affinity towards the targeted p53 protein in the apoptosis pathway. Thus, the objective of this research can provide an insight prediction towards M. oleifera derived bioactive compounds and target apoptosis protein p53 in the structural analysis for compound isolation and in-vivo experiments on the cancer cell line.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.4
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• pp.117-123
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• 2021

Gefitinib, a first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), provides obvious clinical benefit in patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, patients ultimately develop gefitinib resistance which mainly caused by EGFR T790M secondary mutation. In the current study, we investigated whether the root extract of Scutellaria baicalensis (SB) overcomes gefitinib resistance. Gefitinib-resistant H1975 human NSCLC cells (EGFR L858R/T790M double mutant) were treated with gefitinib and/or ethanol extract of SB (ESB) to evaluate the effect of ESB on the gefitinib sensitivity. The cell viability was measured by MTT assay and trypan blue exclusion assay. The colony-forming ability was evaluated by anchorage-dependent colony formation assay. Combined treatment with gefitinib and ESB markedly decreased the cell viability and colony formation than single treatment with gefitinib or ESB in H1975 cells. In addition, cells treated with both gefitinib and ESB exhibited a significant increase of sub-G1 DNA content which indicates apoptotic cells compared with those treated with gefitinib or ESB alone. As a molecular mechanism, combined treatment with gefitinib and ESB strongly downregulated the phosphorylation of ERK and JNK than single treatment with gefitinib or ESB. Taken together, our results demonstrate that ESB sensitizes H1975 cells to gefitinib treatment. We cautiously propose that ESB can be used in combination with gefitinib for the advanced NSCLC patients with acquired resistance to EGFR TKIs.