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Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2
Myoung-Eun Han,Young-Suk Lee,Sun-Yong Baek,Bong-Seon Kim,Jae-Bong Kim,Sae-Ock Oh
International Journal of Molecular Sciences , 2009, DOI: 10.3390/ijms10073033
Abstract: Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2.
LAP2 Is Widely Overexpressed in Diverse Digestive Tract Cancers and Regulates Motility of Cancer Cells
Hyun-Jung Kim, Sun-Hwi Hwang, Myoung-Eun Han, Sungmin Baek, Hey-Eun Sim, Sik Yoon, Sun-Yong Baek, Bong-Seon Kim, Jeong-Hwan Kim, Seon-Young Kim, Sae-Ock Oh
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039482
Abstract: Background Lamina-associated polypeptides 2 (LAP2) is a nuclear protein that connects the nuclear lamina with chromatin. Although its critical roles in genetic disorders and hematopoietic malignancies have been described, its expression and roles in digestive tract cancers have been poorly characterized. Methods To examine the expression of LAP2 in patient tissues, we performed immunohistochemistry and real-time PCR. To examine motility of cancer cells, we employed Boyden chamber, wound healing and Matrigel invasion assays. To reveal its roles in metastasis in vivo, we used a liver metastasis xenograft model. To investigate the underlying mechanism, a cDNA microarray was conducted. Results Immunohistochemistry in patient tissues showed widespread expression of LAP2 in diverse digestive tract cancers including stomach, pancreas, liver, and bile duct cancers. Real-time PCR confirmed that LAP2β is over-expressed in gastric cancer tissues. Knockdown of LAP2β did not affect proliferation of most digestive tract cancer cells except pancreatic cancer cells. However, knockdown of LAP2β decreased motility of all tested cancer cells. Moreover, overexpression of LAP2β increased motility of gastric and pancreatic cancer cells. In the liver metastasis xenograft model, LAP2β increased metastatic efficacy of gastric cancer cells and mortality in tested mice. cDNA microarrays showed the possibility that myristoylated alanine-rich C kinase substrate (MARCKS) and interleukin6 (IL6) may mediate LAP2β-regulated motility of cancer cells. Conclusions From the above results, we conclude that LAP2 is widely overexpressed in diverse digestive tract cancers and LAP2β regulates motility of cancer cells and suggest that LAP2β may have utility for diagnostics and therapeutics in digestive tract cancers.
Regulation of cerebrospinal fluid production by caffeine consumption
Myoung-Eun Han, Hak-Jin Kim, Young-Suk Lee, Dong-Hyun Kim, Joo-Taek Choi, Chul-Sik Pan, Sik Yoon, Sun-Yong Baek, Bong-Seon Kim, Jae-Bong Kim, Sae-Ock Oh
BMC Neuroscience , 2009, DOI: 10.1186/1471-2202-10-110
Abstract: In the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na+, K+-ATPase and increased cerebral blood flow (CBF). In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A1 adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na+, K+-ATPase, in A1 agonist-treated rats.The results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na+, K+-ATPase and CBF.Methylxanthine caffeine is present in many common beverages, and is widely consumed worldwide [1,4]. Caffeine consumption has been estimated to be 76 mg per person per day worldwide, as high as 238 mg per person per day in the United States and Canada, and more than 400 mg per person per day in Sweden and Finland [5,6]. Caffeine is absorbed rapidly after oral administration and distributed to various organs and tissues. In the liver, caffeine is metabolized to dimethyl- and monomethylxanthines, dimethyl and monomethyl uric acids, trimethyl- and dimethylallantoin, and uracil derivatives. Some metabolites of caffeine including 1,3-dimethylxanthine (theophylline) and 1,7-dimethylxanthine (paraxanthine) have pharmacological activity similar to caffeine [4]. The half-life of caffeine is ~5 hours in humans and ~1 hour in rats [4,7].The main mechanism of action of caffei
Direct Engagement of TLR4 in Invariant NKT Cells Regulates Immune Diseases by Differential IL-4 and IFN-γ Production in Mice
Ji Hyung Kim, Hye Sung Kim, Hye Young Kim, Sae Jin Oh, Doo Hyun Chung
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045348
Abstract: During interaction with APCs, invariant (i) NKT cells are thought to be indirectly activated by TLR4-dependently activated APCs. However, whether TLR4 directly activates iNKT cells is unknown. Therefore, the expression and function of TLR4 in iNKT cells were investigated. Flow cytometric and confocal microscopic analysis revealed TLR4 expression on the surface and in the endosome of iNKT cells. Upon LPS stimulation, iNKT cells enhanced IFN-γ production, but reduced IL-4 production, in the presence of TCR signals, depending on TLR4, MyD88, TRIF, and the endosome. However, enhanced TLR4-mediated IFN-γ production by iNKT cells did not affect IL-12 production or CD1d expression by DCs. Adoptive transfer of WT, but not TLR4-deficient, iNKT cells promoted antibody-induced arthritis in CD1d?/? mice, suggesting that endogenous TLR4 ligands modulate iNKT cell function in arthritis. Furthermore, LPS-pretreated WT, but not TLR4-deficient, iNKT cells suppressed pulmonary fibrosis, but worsened hypersensitivity pneumonitis more than untreated WT iNKT cells, indicating that exogenous TLR4 ligands regulate iNKT cell functions in pulmonary diseases. Taken together, we propose a novel direct activation pathway of iNKT cells in the presence of TCR signals via endogenous or exogenous ligand-mediated engagement of TLR4 in iNKT cells, which regulates immune diseases by altering IFN-γ and IL-4 production.
NOD2-mediated Suppression of CD55 on Neutrophils Enhances C5a Generation During Polymicrobial Sepsis
Sae Jin Oh equal contributor,Ji Hyung Kim equal contributor,Doo Hyun Chung
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003351
Abstract: Nucleotide-binding oligomerization domain (NOD) 2 is a cytosolic protein that plays a defensive role in bacterial infection by sensing peptidoglycans. C5a, which has harmful effects in sepsis, interacts with innate proteins. However, whether NOD2 regulates C5a generation during sepsis remains to be determined. To address this issue, cecal ligation & puncture (CLP)-induced sepsis was compared in wild type and Nod2?/? mice. Nod2?/? mice showed lower levels of C5a, IL-10, and IL-1β in serum and peritoneum, but higher survival rate during CLP-induced sepsis compared to wild type mice. Injection of recombinant C5a decreased survival rates of Nod2?/? mice rate during sepsis, whereas it did not alter those in wild type mice. These findings suggest a novel provocative role for NOD2 in sepsis, in contrast to its protective role during bacterial infection. Furthermore, we found that NOD2-mediated IL-10 production by neutrophils enhanced C5a generation by suppressing CD55 expression on neutrophils in IL-1β-dependent and/or IL-1β-independent manners, thereby aggravating CLP-induced sepsis. SB203580, a receptor-interacting protein 2 (RIP2) inhibitor downstream of NOD2, reduced C5a generation by enhancing CD55 expression on neutrophils, resulting in attenuation of polymicrobial sepsis. Therefore, we propose a novel NOD2-mediated complement cascade regulatory pathway in sepsis, which may be a useful therapeutic target.
Agaricus blazei Extract Induces Apoptosis through ROS-Dependent JNK Activation Involving the Mitochondrial Pathway and Suppression of Constitutive NF-κB in THP-1 Cells
Mun-Ock Kim,Dong-Oh Moon,Jin Myung Jung,Won Sup Lee,Yung Hyun Choi,Gi-Young Kim
Evidence-Based Complementary and Alternative Medicine , 2011, DOI: 10.1093/ecam/nep176
Abstract: Agaricus blazei is widely accepted as a traditional medicinal mushroom, and it has been known to exhibit immunostimulatory and anti-cancer activity. However, the apoptotic mechanism in cancer cells is poorly understood. In this study, we have investigated whether A. blazei extract (ABE) exerts antiproliferative and apoptotic effects in human leukemic THP-1 cells. We observed that ABE-induced apoptosis is associated with the mitochondrial pathway, which is mediated by reactive oxygen species (ROS) generation and prolonged c-Jun N-terminal kinase (JNK) activation. In addition, the ABE treatment resulted in the accumulation of cytochrome c in the cytoplasm, an increase in caspase activity, and an upregulation of Bax and Bad. With those results in mind, we found that ABE decreases constitutive NF-κB activation and NF-κB-regulated gene products such as IAP-1 and -2. We concluded that ABE induces apoptosis with ROS-dependent JNK activation and constitutive activated NF-κB inhibition in THP-1 cells.
Doctor’s identity in modern Western society
KIM Ock-Joo
Korean Journal of Medical History , 2005,
Abstract: Two centuries ago doctors perceived themselves quite differently as they do today Doctor’s identity in modern Western society shaped from the modernization of medicine starting in the nineteenth century Modern medicine as practiced today was established from 1800 to the World War I In the eighteenth century three medical groups (physicians surgeons and apothecaries) struggled to elevate their position and to organize their education Surgery and surgical education in hospitals developed greatly while physicians tried to theorize their own medical system in the eighteenth century In the early nineteenth century hospital medicine emerged hospitals moved from the place for the poor and the social inadequate to the center of medical education and research Especially French hospitals became the birth places of clinico-pathology new diagnosis with stethoscope careful observation and the numerical method The influence of the hospital medicine spread from France to England America and other parts of Europe After the birth of clinic in France laboratory medicine emerged in Germany France Britain and the United States Surpassing other nations Germany developed university-centered laboratory research system Most of all the reward and status of the laboratory researchers were established so that they could concentrate on their research Although other countries were influenced by German system and knowledge they did not develop research system at the same degree as Germany Rise of scientific medicine transformed self-perception of doctors Science made a great impact not only on the doctors’ practice of medicine but also on the public’s perception of medicine and doctors In the late nineteenth century new discoveries and new armament of scientific medicine marched through antiseptic surgery tropical medicine new laboratories antitoxin therapies from immunology the rise of pharmaceutical industry and the discovery of X-ray Payment system also was changed with the rise of national health insurance system in Europe Finally the advancement of scientific medicine in the late nineteenth century brought changes in medical education specialization and doctor-patient relationship One of the important changes in doctor-patient relationship occurred between female patients and male obstetrician In the mid-eighteenth century childbearing as expressed in the term “brought to bed ” was women’s business Midwives and women relatives took care of laboring women As scientific medicine arose male doctors began to enter the laboring room previously forbidden area to men As Leavitt showed
Experimental Sciences in Surgery: Harvey Cushing's Work at the Turn of the Twentieth Century
KIM Ock-Joo
Korean Journal of Medical History , 2006,
Abstract: No Abstract Available.
Clinicopathologic characteristics and treatment outcomes of hepatoid adenocarcinoma of the stomach, a rare but unique subtype of gastric cancer
Sun Baek, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
BMC Gastroenterology , 2011, DOI: 10.1186/1471-230x-11-56
Abstract: We consecutively enrolled patients with pathologically proven gastric HAC at Seoul National University Hospital between January 1996 and December 2008 and conducted a retrospective review. Among 15,253 patients with gastric cancer, 26 patients (0.17%) were diagnosed as gastric HAC.Among 26 patients, 22 were male and the median age was 63. Stage at diagnosis was stage IB in 3 patients, stage II in 6 patients, stage III in 7 patients, and stage IV in 10 patients. Eight patients out of 18 patients with stage IB, II, III, and IV relapsed after curative surgery. Relapse-free survival for these patients was 16.67 months. The most common metastatic site was intraabdominal lymph nodes (n = 9), followed by the liver (n = 8). Thirteen patients received palliative chemotherapy. The most commonly used regimen was a combination of fluoropyrimidine and platinum. Partial response was observed in one patient and stable disease in 5 patients. Median overall survival and progression free survival of these patients were 8.03 (95% CI: 6.59-9.47) and 3.47 months (95% CI: 0.65-6.29), respectively.Gastric HAC is a very rare but unique type of stomach cancer. Early detection of this type of cancer is of critical importance to patient prognosis. Additional studies to reveal the biology of this tumor are warranted.Hepatoid adenocarcinoma (HAC) showed a histologic appearance typical of hepatocellular carcinoma, including solid, trabecular, and pseudograndular structures; tumor cells were round or polygonal in shape [1]. HACs have been described in several different organs, including the lung, pancreas, esophagus, ampulla of Vater, colon, urinary bladder, renal pelvis, ovaries, uterus, and cervix [2-12]. The stomach is the organ in which HAC has been most commonly identified. Incidence of HAC is known to be 0.38-0.73%, as reported in a previous study [1,13]Alpha-fetoprotein (AFP) is a fetal serum protein produced by fetal liver and yolk sac cells, and by some fetal gastrointestinal cells [14].
Preservice Teachers’ Sense of Efficacy and Its Sources  [PDF]
Sunjin Oh
Psychology (PSYCH) , 2011, DOI: 10.4236/psych.2011.23037
Abstract: The purpose of this study was to examine several potential sources of preservice teachers’ perceptions of their teaching efficacy during their reading and writing lessons. More specifically, the study explored the relationship between the sources of preservice teachers’ self-efficacy and teachers’ perception of efficacy in the areas of instructional strategies, classroom management, and student engagement. Forty-three preservice teachers in pre-literacy methods courses and fourteen in post-literacy methods courses completed the survey, which consisted of the Teacher Sense of Efficacy Scale (TSES) and Teaching Efficacy Sources Inventory. Paired t-test results showed that preservice teachers’ teaching efficacy increased in the three subscales of instructional strategies, classroom management, and student engagement by the end of the literacy method courses. Efficacy for instructional strategies, classroom management, and student engagement were highly intercorrelated with each other in the pre-test data. The results of multiple regression analysis indicated that personality characteristics, capabilities, motivation, enactive mastery experiences with social/verbal persuasion, and physiological/affective state were significant predictors when efficacy for classroom management was the dependent variable in the post-test data. Findings of this study revealed that preservice teachers’ personality, motivation, and capabilities were one of the important sources to improve their teaching efficacy, in congruence with previous research (Poulou, 2007; Yeung & Watkins, 2000).
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