• Title/Summary/Keyword: P3a

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Impact of Intraoperative Macroscopic Diagnosis of Serosal Invasion in Pathological Subserosal (pT3) Gastric Cancer

  • Kim, Dong Jin;Lee, Jun Hyun;Kim, Wook
    • Journal of Gastric Cancer
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    • v.14 no.4
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    • pp.252-258
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    • 2014
  • Purpose: The macroscopic diagnosis of tumor invasion through the serosa during surgery is not always distinct in patients with gastric cancer. The prognostic impact of the difference between macroscopic findings and pathological diagnosis of serosal invasion is not fully elucidated and needs to be re-evaluated. Materials and Methods: A total of 370 patients with locally advanced pT2 to pT4a gastric cancer who underwent curative surgery were enrolled in this study. Among them, 155 patients with pT3 were divided into three groups according to the intraoperative macroscopic diagnosis of serosal invasion, as follows: serosa exposure (SE)(-) (no invasion, 72 patients), SE(${\pm}$) (ambiguous, 47 patients), and SE(+) (definite invasion, 36 patients), and the clinicopathological features, surgical outcomes, and disease-free survival (DFS) were analyzed. Results: A comparison of the 5-year DFS between pT3_SE(-) and pT2 groups and between pT3_SE(+) and pT4a groups revealed that the differences were not statistically significant. In addition, in a subgroup analysis of pT3 patients, the 5-year DFS was 75.1% in SE(-), 68.5% in SE(${\pm}$), and 39.4% in SE(+) patients (P<0.05). In a multivariate analysis to evaluate risk factors for tumor recurrence, macroscopic diagnosis (hazard ratio [HR], SE(-) : SE(${\pm}$) : SE(+)=1 : 1.01 : 2.45, P=0.019) and lymph node metastasis (HR, N0 : N1 : N2 : N3=1 : 1.45 : 2.20 : 9.82, P<0.001) were independent risk factors for recurrence. Conclusions: Gross inspection of serosal invasion by the surgeon had a strong impact on tumor recurrence in gastric cancer patients. Consequently, the gross appearance of serosal invasion should be considered as a factor for predicting patients' prognosis.

Dephosphorylation of p53 Ser 392 Enhances Trimethylation of Histone H3 Lys 9 via SUV39h1 Stabilization in CK2 Downregulation-Mediated Senescence

  • Park, Jeong-Woo;Bae, Young-Seuk
    • Molecules and Cells
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    • v.42 no.11
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    • pp.773-782
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    • 2019
  • Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, $p21^{Cip1/WAF1}$ is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of $p21^{Cip1/WAF}$. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of $p21^{Cip1/WAF1}$, leading to H3K9me3 and SAHFs formation.

Synthesis and Primary Screening for Growth Inhibitors of L1210 Cells of Cholesteryl p-[3-(2-chloroethyl)-3-nitrosoureido] Phenylthioacetate

  • Kim, Jack-C.;Kim, Min-Sook;Lee, Hyeon-Kyuy
    • Archives of Pharmacal Research
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    • v.6 no.2
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    • pp.115-121
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    • 1983
  • Cholesteryl p-[3-(2-chloroethyl_-3-nitrosoureido] phenylthioaccetate (2) was synthesized : an intermediate, p-[3(2-chloroethyl_-3-nitrosoureido] phenylthioacetic acid (1) is a congener of an antitumor chlorambucil which both the -CH$_{2}$CH$_{2}$-linkage and -N(CH$_{2}$CH$_{2}$Cl)$_{2}$ group of chlorambucil molecule is doubly modified into the respective -S-linkage and -NH-CO-NNO-CH$_{2}$CH$_{2}$CL group. The attackment of cholesterol moiety as a carrier group to p-[3-(2-chloroethyl-3nitrosoureido] phenylthioacetic acid was accomplished through the esterification of cholesterol with p-[3-(2-chloroethyl-3-nitrosoureido] phenylthioacetyl chloride which was obtained from the treatment of p-[3-(2-chloroethyl)-3-nitrosourei-do] phenylthioaceticacid with SOCL$_{2}$, p-[3-(2-chloroethyl)ureido]]-phenythioacetic acid was nitrosated with NaNO$_{2}$ IN 98-100% HCOOH to give exclusively p-[3-(2-chloroethyl_-3-nitrosoureido] phenylthioacetic acid. Antitumor evaluation of compounds, 1 and 2 on L 1210 leukemia did show significant activity (ED$_{40}$ : 1.14.mu./ml and 8.4.mu.g/ml, repectively). Further studies were subjected..

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p-n Heterojunction Composed of n-ZnO/p-Zn-doped InP

  • Shim, Eun-Sub;Kang, Hong-Seong;Kang, Jeong-Seok;Pang, Seong-Sik;Lee, Sang-Yeol
    • Transactions on Electrical and Electronic Materials
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    • v.3 no.1
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    • pp.1-3
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    • 2002
  • A p-n junction was obtained by the deposition of an n-type ZnO thin film on a p-type Zn-doped InP substrate. The Zn-doped InP substrate has been made by the diffusion of Zn with sealed ampoule technique. The ZnO deposition process was performed by pulsed laser deposition (PLD). The p-n junction was formed and showed typical I-V characteristics. We will also discuss about the realization of an ultraviolet light-emitting diode (LED). The structure of n-ZnO/p-Zn-doped InP could be a good candidate for the realization of an ultraviolet light-emitting diode or an ultraviolet laser diode.

The Relationship between Health Belief.Self-efficacy and Exercise.Diet Compliance in Coronary Heart Disease Patients (관상동맥질환자의 건강신념 및 자기효능감과 운동 및 식이요법 이행과의 관계)

  • Nam, Myung-Hee;Kim, Chung-Nam;Oh, Yun-Jung
    • Research in Community and Public Health Nursing
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    • v.8 no.2
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    • pp.262-276
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    • 1997
  • This study evaluates the relationship between health belief. self-efficacy and exercise and diet compliance in coronary heart disease patients. The study subjects were 96 CHD patients who visited the outpatient clinic at 3 general hospitals in Taegu city from April 3, 1997 to May 3, 1997. Data was collected by the researcher and two registered nurses who work at a cardiac outpatient clinic. Face-to-face interview was conducted. Moon's health belief scale(l990) and Hicky and others' Cardiac Diet Self-Efficacy Instrument (CDSEI, 1992), Cardiac Exercise Self-Efficacy Instrument (CESEI, 1992) were used. The instrument developed by the researcher based on the reference review was used to measure exercise and diet compliance. The data were analyzed by using descriptive statistics, Pearson correlation coefficient, t-test, ANOVA, Tukey verification and Stepwise multiple regression with the SAS program. The results of this study were as follows; 1. The degree of health belief(score range: 1-4) perceived benefit: 3.06 barrier: 2.04 severity: 2.93 2. The degree of self-efficacy(score range: 1-5) exercise self-efficacy: 2.91 diet self-efficacy: 3.32 3. The degree of compliance (score range: 1-4) exercise compliance: 2.34 diet compliance: 2.95 4. The exercise compliance had a positive correlation with perceived benefit(r=0.5327, p=0. 0001), severity(r=0.2780, p=0.0061), exercise self-efficacy(r=0.6675, p=0.0001), and a negative correlation with barrier{r= -0.4236, p=0.0001). The diet compliance had a positive correlation with perceived benefit (r=0.6439, p=0.0001), severity(r=0.4244, p=0.0001), diet self-efficacy(r=0.6629, p=0.0001), and a negative correlation with barrier{r= -0.5098, p=0.0001). 5. According to pt's education level, (F=3.02, p=0.0336), received massage from mass media on exercise and diet(t=3.81, p=0.0002), presence of cardiac patients in the family members or friends(t=2.00, p=0.0478), created significant differences in exercise compliance. According to occuption(F=3.03, p=0.0215), hospitalized experience(t=4.59, p=0.0000), presence of chest pain(t=3.63, p=0.0005), there was also a significant difference in diet compliance. 6. The combination of exercise self-efficacy, perceived benefit and pt's education level explained 50.18% of the variance in exercise compliance. The combination of diet self-efficacy, perceived benefit and barrier explained 56.76% of the variance in diet compliance. On the basis of the above findings, the follow ing recommendations are suggested: 1. To promote the exercise. diet compliance for CHD patients, a well organized health teaching and nursing intervention program should be developed. 2. More research is needed to investigate other variables affecting exercise and diet compliance of CHD patients. 3. To promote self-efficacy and a positive health belief in CHD patients, a well organized and an approachable nursing intervention program should be developed. 4. Factors other than diet. exercise compliance should be evaluated to discover the impact on CHD patients.

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Novel p104 protein regulates cell proliferation through PI3K inhibition and p27Kip1 expression

  • Han, Seung-Jin;Lee, Jung-Hyun;Choi, Ki-Young;Hong, Seung-Hwan
    • BMB Reports
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    • v.43 no.3
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    • pp.199-204
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    • 2010
  • The protein p104 was first isolated as a binding partner of the Src homology domain of phospholipase C$\gamma$1, and has been shown to associate with p85$\alpha$, Grb2. The ectopic expression of p104 reduced cellular growth rate, which was also achieved with the overexpression of only the proline-rich region of p104. The proline-rich region of p104 has been found to inhibit the colony formation of platelet-derived growth factor BB-stimulated NIH3T3 cells and MCF7 cancer cells on soft agar. Mutagenesis analysis showed that the second and third proline-rich regions are essential for growth control, as well as for interaction with p85$\alpha$. Overexpression of p104 increased the level of the cyclin-dependent kinase inhibitor, $p27^{Kip1}$, and inhibited the activity of phosphoinositide 3-kinase (PI3K). In summary, p104 interacts with p85$\alpha$ and is involved in the regulation of $p27^{Kip1}$ expression for the reduction of cellular proliferation.

Expression of Porcine Acid-labile Subunit (pALS) of the 150-kilodalton Ternary Insulin-like Growth Factor Complex and Initial Characterization of Recombinant pALS Protein

  • Lee, Dong-Hee;Chun, Choa;Kim, Sang-Hoon;Lee, C.-Young
    • BMB Reports
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    • v.38 no.2
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    • pp.225-231
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    • 2005
  • Acid-labile subunit (ALS) is a component of the 150-kDa insulin-like growth factor-binding protein-3 (IGFBP-3) complex, which, by sequestering the majority of IGFs-I and -II and thereby prolonging the half-life of them in plasma, serves as a circulating reservoir of IGFs in mammalian species. A pGEX-2T plasmid and a baculovirus expression constructs harboring a coding sequence for glutathione-S transferase (GST)-porcine ALS (pALS) fusion protein were expressed in BL21(DE3) E. coli and Sf9 insect cells, respectively. The expressed protein was purified by glutathione or Ni-NTN affinity chromatography, followed by cleavage of the fusion protein using Factor Xa. In addition, pALS and hIGFBP-3 were also produced in small amounts in the Xenopus oocyte expression system which does not require any purification procedure. A 65-kDa pALS polypeptide was obtained following the prokaryotic expression and the enzymatic digestion, but biochemical characterization of this polypeptide was precluded because of an extremely low expression efficiency. The baculovirus-as well as Xenopus-expressed pALS exhibited the expected molecular mass of 85 kDa which was reduced into 75 and 65 kDa following deglycosylation of Asn-linked carbohydrates by Endo-F glycosidase, indicating that the expressed pALS was properly glycosylated. Moreover, irrespective of the source of pALS, the recombinant pALS and hIGFBP-3 formed a 130-kDa binary complex which could be immunoprecipitated by anti-hIGFBP-3 antibodies. Collectively, results indicate that an authentic pALS protein can be produced by the current expression systems.

miR-380-3p promotes β-casein expression by targeting αS1-casein in goat mammary epithelial cells

  • Ning Song;Jun Luo;Lian Huang;Xiaoying Chen;Huimin Niu;Lu Zhu
    • Animal Bioscience
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    • v.36 no.10
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    • pp.1488-1498
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    • 2023
  • Objective: αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods: αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results: Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3'-untranslated region (3'UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion: miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.

Combined Detection of Serum MiR-221-3p and MiR-122-5p Expression in Diagnosis and Prognosis of Gastric Cancer

  • Zhang, Yan;Huang, Huifeng;Zhang, Yun;Liao, Nansheng
    • Journal of Gastric Cancer
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    • v.19 no.3
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    • pp.315-328
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    • 2019
  • Purpose: To investigate the clinical value of serum miR-221-3p and miR-122-5p expression levels in the diagnosis and prognosis of gastric cancer. Materials and Methods: Serum samples from 141 gastric cancer cases (gastric cancer group), 110 gastric polyps (gastric polyp group), and 75 healthy people (healthy control) were used to detect miR-221-3p and miR-122-5p expression using real-time reverse transcription polymerase chain reaction. Results: Serum miR-221-3p expression was significantly higher in the gastric cancer group than in the gastric polyp group, and it was significantly lower than that before operation. The miR-221-3p expression was significantly higher in the death group than in the survival group. The proliferation and migration ability significantly increased and the apoptosis rate significantly decreased by miR-221-3p transfection in gastric cancer cells. In contrast, the function of miR-122-5p in gastric cancer cells was opposite of miR-221-3p. Serum miR-221-3p expression was negatively correlated with that of miR-122-5p in gastric cancer. Serum miR-221-3p and miR-122-5p expressions were significantly correlated with the degree of differentiation, tumor, node, metastasis stage, lymph node metastasis, and invasion depth. miR-221-3p and miR-122-5p expression levels were independent prognostic factors for postoperative gastric cancer. In the diagnosis and predicting prognosis of gastric cancer, receiver operating characteristic analysis revealed that the area under curve of combined detection of serum miR-221-3p and miR-122-5p expression had a greater diagnostic effect than either single maker. Conclusions: The miR-221-3p and miR-122-5p are involved in the development of gastric cancer, and they have important clinical values in gastric cancer diagnosis and prognosis.