• Korean Journal of Clinical Laboratory Science
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• v.45 no.1
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• pp.32-36
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• 2013

The thyroid is the organ that has the greatest risk of malignant tumors among the endocrine tumors. The papillary carcinoma occupies 80% of the entire thyroid tumors. Immunohistochemical staining of galectin-3 has usually been used in differentiating papillary carcinoma and follicular carcinoma. The p53 gene of the cell cycle is a tumor suppressor gene acting in on the control points. The cyclin D1 genes in the cell cycle, involved in the implementation of G1 and S phase, plays an important role in the progression of thyroid tumors. This research compares and analyzes correlation between papillary carcinoma, follicular carcinoma, p53, cyclin D1 and galectin-3 gene expression patterns. In a total of 30 cases from papillary carcinoma, 21 cases from p53 (70%), 27 cases in galectin-3 (90%), and 26 cases in cyclin D1 (86.7%) showed positive rate. The galectin-3 staining investigated, showed a significant difference between a papillary carcinoma and a follicular carcinoma. Follicular carcinoma from 15 cases, p53 in 13 cases (86.7%), galectin-3 in 5 cases (33.3%) and cyclin D1 in 12 cases (80%) showed a positive rate. The cyclin D1 in follicular carcinoma and staining between the p53 that had correlation was also investigated. In this study, as the examples of the expression of the 27 cases of galectin-3 (90%) in papillary carcinoma and 5 cases in follicular carcinoma (33.3%) indicate, it was concluded that there is a difference in the expression on both carcinoma. In addition, cyclin D1 and p53 has a positive rate in follicular carcinoma, when cyclin D1 in 12 cases (80%), there was a significant correlation that was investigated. Distinguishing between papillary carcinoma and follicular carcinoma can be identified by the expression of galectin-3. It is considered to get results that are more accurate in follicular carcinoma diagnosis depending on whether the cyclin D1 and p53 is expressed or not.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2325-2328
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• 2012

Background: Cyclin D1 (CCND1) is critical in the transition of the cell cycle from G1 to S phases and unbalanced cell cycle regulation is a hallmark of carcinogenesis. A number of studies conducted to assess the association between CCND1 G870A polymorphism and susceptibility to lung cancer have yielded inconsistent and inconclusive results. In the present study, the possible association above was assessed by a meta-analysis. Methods: Eligible articles were identified for the period up to November 2011. Pooled odds ratios (OR) with 95% confidence intervals (95%CI) were appropriately derived from fixed effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from the Hardy-Weinberg equilibrium (HWE) was performed. Results: Ten case-control studies with a total of 10,548 subjects were eligible. At the overall analysis the CCND1 870A allele appeared to be associated with elevated lung cancer risk (for allele model, pooled OR = 1.24, 95% CI: 1.08-1.44, P = 0.004; for homozygous model, pooled OR = 1.45, 95% CI: 1.14-1.84, P = 0.003; for recessive model, pooled OR = 1.29, 95% CI: 1.06-1.58, P = 0.013; for dominant model, pooled OR = 1.33, 95% CI: 1.08-1.65, P = 0.009). Subgroup analyses by ethnicity and sensitivity analysis further pointed to associations, particularly in Asians. Conclusion: This meta-analysis suggests that the A allele of CCND1 G870A polymorphism confers additional lung cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2711-2715
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• 2013

Background: Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. Materials and Methods: In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled Results: Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. Conclusions: The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies.

• The Plant Pathology Journal
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• v.30 no.2
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• pp.136-150
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• 2014

Although multiple transcription factors (TFs) have been characterized via mutagenesis to understand their roles in controlling pathogenicity and infection-related development in Magnaporthe oryzae, the causal agent of rice blast, if and how forkhead-box (FOX) TFs contribute to these processes remain to be characterized. Four putative FOX TF genes were identified in the genome of M. oryzae, and phylogenetic analysis suggested that two of them (MoFKH1 and MoHCM1) correspond to Ascomycota-specific members of the FOX TF family while the others (MoFOX1 and MoFOX2) are Pezizomycotina-specific members. Deletion of MoFKH1 (${\Delta}Mofkh1$) resulted in reduced mycelial growth and conidial germination, abnormal septation and stress response, and reduced virulence. Similarly, ${\Delta}Mohcm1$ exhibited reduced mycelial growth and conidial germination. Conidia of ${\Delta}Mofkh1$ and ${\Delta}Mohcm1$ were more sensitive to one or both of the cell cycle inhibitors hydroxyurea and benomyl, suggesting their role in cell cycle control. On the other hand, loss of MoFOX1 (${\Delta}Mofox1$) did not show any noticeable changes in development, pathogenicity, and stress response. Deletion of MoFOX2 was not successful even after repeated attempts. Taken together, these results suggested that MoFKH1 and MoHCM1 are important in fungal development and that MoFKH1 is further implicated in pathogenicity and stress response in M. oryzae.

• Journal of Life Science
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• v.18 no.1
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• pp.96-102
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• 2008

Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the anti-cancer potency of piceatannol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail. In the present study, we investigated further possible mechanisms by which piceatannol exerts its anti-proliferative action in cultured human leukemia U937 cells. Exposure of U937 cells to piceatannol resulted in growth inhibition and induction of apoptosis as measured by MTT assay and flow cytometry analysis, which was associated with S phase arrest of the cell cycle. Piceatannol treatment markedly inhibited the activity of telomerase, and the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1), main determinants of the telomerase enzymatic activity, were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. However, the levels of cyclooxygenases (COXs) expression and prostaglandin E2 (PGE2) release were not changed in piceatannol-treated U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of piceatannol.

• Journal of Embryo Transfer
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• v.18 no.3
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• pp.263-267
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• 2003

This study was carried out to test the efficacy of pharmacological inhibitors of the cell cycle transition in keeping bovine oocytes at the germinal vesicle(GV) stage and the reversibility of this inhibition. Bovine oocytes were incubated for 22∼24 hrs in the presence of various inhibitors : cycloheximide (2$\mu\textrm{g}$/$m\ell$), 6-DMAP (2 mM), and roscovitine (50$\mu$M). Bovine oocytes cultured with any of the inhibitors were significantly blocked at the GV stage. Reversibility of pharmacological inhibitors was assessed by culturing oocytes an additional 22∼24 hours in inhibitor-free medium. Examination of oocytes revealed that the inhibitory effect was fully reversible and effect of resuming meiotic progression on nuclear maturation varied according to the various inhibitors. This study suggests that cycloheximide, 6-DMAP and roscovitine can be applied to control meiotic arrest and resumption in maturation culture of bovine oocytes in vitro. More investigations are needed to better understand how the cell cycle of oocyte is blocked without problems to future developmental competence.

• Journal of Gastric Cancer
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• v.22 no.4
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• pp.348-368
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• 2022

Purpose: Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. Materials and Methods: The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. Results: The PLK2 C_rs15009-C_rs963615 haplotype was under-represented in the GC group compared to that in the control group (P_corr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM T_rs228589-A_rs189037-G_rs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. Conclusions: PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.163-170
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• 2006

Nardostachyos Rhizoma (N. Rhizoma) belonging to the family Valerianaceae has been anti-arrhythmic effect, and sedation to the central nerve and a smooth muscle. We reported that the water extract of N. Rhizoma induced apoptotic cell death and differentiation in human promyelocytic leukemia (HL-60) cells. Cytotoxicity of N. Rhizoma was detected only in HL-60 cells (IC50 is about 200 ${\mu}g/ml$). The cytotoxic activity of N. Rhizoma in HL-60 cells was increased in a dose-dependent manner. We used several measures of apoptosis to determine whether these processes were involved in N. Rhizoma-induced apoptotic cell death. The high-dose (200 ${\mu}g/ml$) treatment of N. Rhizoma to HL-60 cells showed cell shrinkage, cell membrane blobbing, apoptotic bodies, and the fragmentation of DNA, suggesting that these cells underwent apoptosis. Treatment of HL-60 cells with N. Rhizoma time-dependently induced activation of caspase-3, caspase-8, and caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase. Also, we investigated the effect of N. Rhizoma on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells was determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide assay, respectively. N. Rhizoma induced the differentiation of HL-60 at the low-dose (100 ${\mu}g/ml$) treatment, as shown by increased expression of differentiation surface antigen CD11b, but not CDl4 and increased reducing activity of NBT. When HL-60 cells were treated with N. Rhizoma at concentration of $50{\mu}g/ml\;and\;100{\mu}g/ml$, NBT-reducing activities induced approximately 1.5-fold and 20.0-fold as compared with the control. In contrast, HL-60 cells treated with the N. Rhizoma-ATRA combination showed markedly elevated levels of 26.3-fold at $50{\mu}g/ml$ N. Rhizoma-0.1 ${\mu}M$ ATRA combination and 27.5-fold at 50 ${\mu}g/ml$ N. Rhizoma-0.2 ${\mu}M$ ATRA combination than when treated with N. Rhizoma alone or ATRA alone. It may be that N. Rhizoma plays important roles in synergy with ATRA during differentiation of HL-60 cells. DNA flow-cytometry indicated that N. Rhizoma markedly induced a G1 phase arrest of HL-60 cells. N. Rhizoma-treated HL-60 cells increased the cell population in G1 phase from 32.71% to 42.26%, whereas cell population in G2/M and S phases decreased from 23.61% to 10.33% and from 37.78% to 33.98%, respectively. We examined the change in the $p21^{WAF1/Cip1}\;and\;p27^{Kip1}$ proteins, which are the CKIs related with the G1 phase arrest. The expression of the CDK inhibitor $p27^{Kip1},\;but\;not\;p21^{WAF1/Cip1}$ were markedly increased by N. Rhizoma. Taken together, these results demonstrated that N. Rhizoma induces apoptotic cell death through activation of caspase-3, and potently inhibits the proliferation of HL-60 cells via the G1 phase cell cycle arrest in association with $p27^{Kip1}$ and granulocytic differentiation induction .

• BMB Reports
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• v.51 no.7
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• pp.350-355
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• 2018

HnRNPK is a multifunctional protein that participates in chromatin remodeling, transcription, RNA splicing, mRNA stability and translation. Here, we uncovered the function of hnRNPK in regulating the proliferation and differentiation of myoblasts. hnRNPK was mutated in the C2C12 myoblast cell line using the CRISPR/Cas9 system. A decreased proliferation rate was observed in hnRNPK-mutated cells, suggesting an impaired proliferation phenotype. Furthermore, increased G2/M phase, decreased S phase and increased sub-G1 phase cells were detected in the hnRNPK-mutated cell lines. The expression analysis of key cell cycle regulators indicated mRNA of Cyclin A2 was significantly increased in the mutant myoblasts compared to the control cells, while Cyclin B1, Cdc25b and Cdc25c were decreased sharply. In addition to the myoblast proliferation defect, the mutant cells exhibited defect in myotube formation. The myotube formation marker, myosin heavy chain (MHC), was decreased sharply in hnRNPK-mutated cells compared to control myoblasts during differentiation. The deficiency in hnRNPK also resulted in the repression of Myog expression, a key myogenic regulator during differentiation. Together, our data demonstrate that hnRNPK is required for myoblast proliferation and differentiation and may be an essential regulator of myoblast function.

• 한국신재생에너지학회:학술대회논문집
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• 2007.11a
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• pp.17-18
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• 2007

Solid oxide fuel cells are clean, pollution-free technology for the electrochemical generation of electricity at high efficiency. Specially, the polarization resistance between electrolyte and electrode of SOFC unit cell is of importance, because it is desirable to develop SOFC operating at intermediate temperature below $800^{\circ}C$. The LSCF cathode prepared using modified oxalate method was investigated with different electrolyte. A precursor was prepared with oxalic acid, ethanol and $NH_4OH$ solution. The LSCF precursor was prepared at $80^{\circ}C$, and pH control was 2, 6, 8, 9 and 10. The precursor powder was calcined at $800^{\circ}C$, $1000^{\circ}C$ and $1200^{\circ}C$ for 4hrs. The crystal of LSCF powders show single phase at pH 2, 6, 8 and 9, and the average particle size was about $3{\mu}m$. The LSCF cathode with heat treatment at $1200^{\circ}C$ showed a plot of electric conductivity versus temperature. Unit cell prepared from the LSCF cathode, buffer layer between cathode and electrolyte and the LSGM, YSZ, ScSZ and CeSZ electrolyte. Also interface reaction between LSCF, buffer layer and electrolyte were measured by EPMA and the polarization resistance for unit cell with cycle measure using a Solatron 1260 analyzer.