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Hee Jun Cho,
Kyoung Eun Baek, In-Kyu Kim,
Sun-Mi Park,
Yeong-Lim Choi,
In-Koo Nam,
Seung-Ho Park,
Min-Ju Im,
Jong-Min Yoo,
Ki-Jun Ryu,
Young Taek Oh,
Soon-Chan Hong,
Oh-Hyung Kwon,
Jae Won Kim,
Chang Won Lee,
Jiyun Yoo
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ABSTRACT: Rho GDP dissociation inhibitor 2 (RhoGDI2) was initially identified as a regulator of the Rho family of GTPases. Our recent works suggest that RhoGDI2 promotes tumor growth and malignant progression, as well as enhances chemoresistance in gastric cancer. Here, we delineate the mechanism by which RhoGDI2 promotes gastric cancer cell invasion and chemoresistance using two-dimensional gel electrophoresis (2-DE) on proteins derived from a RhoGDI2-overexpressing SNU-484 human gastric cancer cell line and control cells. Differentially expressed proteins were identified using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). In total, 47 differential protein spots were identified; 33 were upregulated, and 14 were downregulated by RhoGDI2 overexpression. Upregulation of SAE1, Cathepsin D, Cofilin1, CIAPIN1, and PAK2 proteins was validated by Western blot analysis. Loss-of-function analysis using small interference RNA (siRNA) directed against candidate genes reveals the need for CIAPIN1 and PAK2 in RhoGDI2-induced cancer cell invasion and Cathepsin D and PAK2 in RhoGDI2-mediated chemoresistance in gastric cancer cells. These data extend our understanding of the genes that act downstream of RhoGDI2 during the progression of gastric cancer and the acquisition of chemoresistance.
Journal of Proteome Research 02/2012; 11(4):2355-64. · 5.11 Impact Factor
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Hee Jun Cho,
Kyoung Eun Baek,
In-Koo Nam,
Sun-Mi Park, In-Kyu Kim,
Seung-Ho Park,
Min-Ju Im,
Ki-Jun Ryu,
Jong-Min Yoo,
Soon-Chan Hong,
Jae Won Kim,
Chang Won Lee,
Jiyun Yoo
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ABSTRACT: Rho GDP dissociation inhibitor 2 (RhoGDI2) is a regulator of the Rho family GTPases. Recent work from our laboratory suggests that RhoGDI2 expression potentially enhances resistance to cisplatin as well as promotes tumor growth and malignant progression in gastric cancer. In this study, we demonstrate that phospholipase C-gamma (PLCγ) is required for RhoGDI2-mediated cisplatin resistance and cancer cell invasion in gastric cancer. The levels of phosphorylated PLCγ are markedly enhanced in RhoGDI2-overexpressing SNU-484 cells and, by contrast, repressed in RhoGDI2-depleted MKN-28 cells. Depletion of PLCγ expression or inhibition of its activity not only significantly increases cisplatin-induced apoptosis but also suppresses the invasive ability of RhoGDI2-overexpressing SNU-484 cells. Taken together, our results suggest that PLCγ plays a key role in RhoGDI2-mediated cisplatin resistance and cell invasion in gastric cancer cells.
Biochemical and Biophysical Research Communications 10/2011; 414(3):575-80. · 2.48 Impact Factor
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Hee Jun Cho,
Kyoung Eun Baek,
Sun-Mi Park, In-Kyu Kim,
In-Koo Nam,
Yeong-Lim Choi,
Seung-Ho Park,
Min-Ju Im,
Jungil Choi,
Jinhyun Ryu,
Jae Won Kim,
Chang Won Lee,
Sang Soo Kang,
Jiyun Yoo
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ABSTRACT: Rho GDP dissociation inhibitor (RhoGDI)2 has been identified as a regulator of Rho family GTPase. Recently, we suggested that RhoGDI2 could promote tumor growth and malignant progression in gastric cancer. In this study, we demonstrate that RhoGDI2 contributes to another important feature of aggressive cancers, i.e., resistance to chemotherapeutic agents such as cisplatin. Forced expression of RhoGDI2 attenuated cisplatin-induced apoptosis, whereas RhoGDI2 depletion showed opposite effects in vitro. Moreover, the increased anti-apoptotic effect of RhoGDI2 on cisplatin was further validated in RhoGDI2-overexpressing SNU-484 xenograft model in nude mice. Furthermore, we identified Bcl-2 as a major determinant of RhoGDI2-mediated cisplatin resistance in gastric cancer cells. Depletion of Bcl-2 expression significantly increased cisplatin-induced apoptosis in RhoGDI2-overexpressing gastric cancer cells, whereas overexpression of Bcl-2 blocked cisplatin-induced apoptosis in RhoGDI2-depleted gastric cancer cells. Overall, these findings establish RhoGDI2 as an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk in gastric cancer.
Cancer letters 06/2011; 311(1):48-56. · 4.86 Impact Factor
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Hee Jun Cho,
Sun-Mi Park,
Eun Mi Hwang,
Kyoung Eun Baek, In-Kyu Kim,
In-Koo Nam,
Min-Ju Im,
Seung-Ho Park,
Seran Bae,
Jae-Yong Park,
Jiyun Yoo
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ABSTRACT: Gadd45b has been known as a positive mediator of apoptosis induced by certain cytokines and oncogenes. Here, we identified Gadd45b as an effector of Fas-induced apoptosis and found that p38-mediated Rb hyperphosphorylation is one of the mechanisms of Fas-induced apoptosis in murine hepatocyte AML12 cells. Gadd45b has been shown to activate p38 through its physical interaction with MTK1 and induce apoptosis. However, in this study, we have showed that the function of Gadd45b during Fas-induced apoptosis in AML12 cells is different from that reported in previous studies. Depletion of Gadd45b expression did not inhibit the phosphorylation of p38, but it suppressed p38-mediated Rb phosphorylation and apoptosis in response to Fas stimulation by reducing the interaction between p38 and Rb. Ectopic expression of Gadd45b was sufficient to enhance this interaction. These findings suggest that Gadd45b mediates p38-induced Rb phosphorylation by enhancing the interaction between p38 and Rb during Fas-induced apoptosis in murine hepatocytes.
Journal of Biological Chemistry 08/2010; 285(33):25500-5. · 4.77 Impact Factor
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Hee Jun Cho,
Sun-Mi Park,
Eun Mi Hwang,
Kyoung Eun Baek, In-Kyu Kim,
In-Koo Nam,
Min-Ju Im,
Seung-Ho Park,
Seran Bae,
Jae-Yong Park,
Jiyun Yoo
[show abstract]
[hide abstract]
ABSTRACT: Gadd45b has been known as a positive mediator of apoptosis induced by certain cytokines and oncogenes. Here, we identified
Gadd45b as an effector of Fas-induced apoptosis and found that p38-mediated Rb hyperphosphorylation is one of the mechanisms
of Fas-induced apoptosis in murine hepatocyte AML12 cells. Gadd45b has been shown to activate p38 through its physical interaction
with MTK1 and induce apoptosis. However, in this study, we have showed that the function of Gadd45b during Fas-induced apoptosis
in AML12 cells is different from that reported in previous studies. Depletion of Gadd45b expression did not inhibit the phosphorylation
of p38, but it suppressed p38-mediated Rb phosphorylation and apoptosis in response to Fas stimulation by reducing the interaction
between p38 and Rb. Ectopic expression of Gadd45b was sufficient to enhance this interaction. These findings suggest that
Gadd45b mediates p38-induced Rb phosphorylation by enhancing the interaction between p38 and Rb during Fas-induced apoptosis
in murine hepatocytes.
Journal of Biological Chemistry 08/2010; 285(33):25500-25505. · 4.77 Impact Factor
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Hee Jun Cho,
Kyoung Eun Baek,
Sun-Mi Park, In-Kyu Kim,
Yeong-Lim Choi,
Hye-Jung Cho,
In-Koo Nam,
Eun Mi Hwang,
Jae-Yong Park,
Jae Yoon Han,
Sang Soo Kang,
Dong Chul Kim,
Won Sup Lee,
Mi-Ni Lee,
Goo Taeg Oh,
Jae Won Kim,
Chang Won Lee,
Jiyun Yoo
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ABSTRACT: Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of Rho family GTPase. However, there is currently no direct evidence suggesting whether RhoGDI2 activates or inhibits Rho family GTPase in vivo (and which type), and the role of RhoGDI2 in tumor remains controversial. Here, we assessed the effects of RhoGDI2 expression on gastric tumor growth and metastasis progression.
Proteomic analysis was done to investigate the tumor-specific protein expression in gastric cancer and RhoGDI2 was selected for further study. Immunohistochemistry was used to detect RhoGDI2 expression in clinical samples of primary gastric tumor tissues which have different pathologic stages. Gain-of-function and loss-of-function approaches were done to examine the malignant phenotypes of the RhoGDI2-expressing or RhoGDI2-depleting cells.
RhoGDI2 expression was correlated positively with tumor progression and metastasis potential in human gastric tumor tissues, as well as cell lines. The forced expression of RhoGDI2 caused a significant increase in gastric cancer cell invasion in vitro, and tumor growth, angiogenesis, and metastasis in vivo, whereas RhoGDI2 depletion evidenced opposite effects.
Our findings indicate that RhoGDI2 is involved in gastric tumor growth and metastasis, and that RhoGDI2 may be a useful marker for tumor progression of human gastric cancer.
Clinical Cancer Research 05/2009; 15(8):2612-9. · 7.74 Impact Factor
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Robotica. 01/2009; 27:959.
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Robotica. 01/2009; 27:853-859.
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ABSTRACT: The aim of this study was to assess whether nestin is expressed during differentiation of endothelial progenitor cells (EPCs) obtained from human umbilical cord blood (HUCB), and nestin expression is changed in hypoxia-conditioned culture of human umbilical vein endothelial cells (HUVECs).
Among deliveries at our institute, 20 normal pregnant women who delivered by cesarean section at 37-40 weeks' gestation were selected. HUCB mononuclear cells (MNCs) from HUCB were isolated and cultivated. After characterization of CXCR4/KDR/CD34 positive cells (EPCs) by flow cytometry and fluorescent chemical staining, EPC culture was continued through day 10 for differentiation to outgrowth endothelial cell (OEC). For identification of EPC and OEC, RT-PCR was performed for each specific cell markers, such as AC133, CD45, CXCR4, CDH5, vWF, eNOs, CD34, and Flt 1. HUVECs were isolated from human umbilical cord veins by collagenase treatment. Culture of HUVEC in hypoxic and normoxic conditions was performed for 24 h. Nestin expression in EPCs, OECs and HUVECs was detected by RT-PCR and Western blotting.
Western blot analysis and RT-PCR revealed that nestin was not expressed in EPC, but well expressed in OECs and HUVECs. During 24 h of HUVEC culture, time course gene expression of VEGF was significantly increased, but nestin was not changed.
Our results showed that nestin could be used as a new differentiation marker of EPCs, and hypoxic stimuli did not directly affect nestin gene expression.
Acta Obstetricia Et Gynecologica Scandinavica 02/2008; 87(6):643-51. · 1.77 Impact Factor
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ABSTRACT: The state-of-the-art FastSLAM has been shown to cause a particle depletion problem while performing simultaneous localization and mapping for mobile robots. As a result, it always produces over-confident estimates of uncertainty as time progresses. This particle depletion problem is mainly due to the resampling process in FastSLAM, which tends to eliminate particles with low weights. Therefore, the number of particles to perform loop-closure decreases, which makes the performance of FastSLAM degenerate. The resampling process has not been thoroughly analyzed even though it is the main reason for the particle depletion problem. In this paper, standard resampling algorithms (systematic residual and partial resampling), and a rank-based resampling applying genetic algorithms are analyzed using computer simulations. For the thorough analysis, several performance measures are used such as effective sample size, the number of distinct particles, root mean square (RMS) errors, and complexity. According to the simulation results, all resampling algorithms could not resolve the particle depletion problem.
Robot and Human interactive Communication, 2007. RO-MAN 2007. The 16th IEEE International Symposium on; 09/2007
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ABSTRACT: In the present study, we examined the relationship between average fish consumption, as well as the type of fish consumed and levels of mercury in the blood of pregnant women. We also performed follow-up studies to determine if blood mercury levels were decreased after counseling and prenatal education. To examine these potential relationships, pregnant women were divided into two groups: a study group was educated to restrict fish intake, whereas a control group did not receive any prenatal education regarding fish consumption. We measured blood mercury level and performed follow-up studies during the third trimester to examine any differences between the two groups. Out of the 63 pregnant women who participated in our study, we performed follow- up studies with 19 pregnant women from the study group and 12 pregnant women from control group. The average initial blood mercury level of both groups was 2.94 microg/L, with a range of 0.14 to 10.75 microg/L. Blood mercury level in the group who ate fish more than four times per month was significantly higher than that of the group who did not consume fish (p = 0.02). In follow-up studies, blood mercury levels were decreased in the study group but slightly increased in the control group (p = 0.014). The maternal blood mercury level in late pregnancy was positively correlated with mercury levels of cord blood (r = 0.58, p = 0.047), which was almost twice the level found in maternal blood. Pregnant women who consume a large amount of fish may have high blood mercury levels. Further, cord blood mercury levels were much higher than that of maternal blood. Because the level of fish intake appears to influence blood mercury level, preconceptual education might be necessary in order decrease fish consumption.
Yonsei Medical Journal 11/2006; 47(5):626-33. · 1.14 Impact Factor
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ABSTRACT: Ovarian cysts are the most frequent, prenatally diagnosed intra-abdominal cysts. Fetal ovarian cyst often presents complication such as torsion and seems to be an indication for surgical intervention. In this study, we reviewed pre- and post-natal medical records and ultrasonography of 17 fetuses that were diagnosed with ovarian cysts. In a total of 17 cases, postnatal surgery was performed in 7 infants. Of these cases, four cases of ovarian cyst torsion were confirmed. In the remaining 10 fetuses, one case regressed completely during pregnancy, and the other nine cases including two complex cysts resolve spontaneously after birth. Postnatal symptomatic cysts or cysts with a diameter greater than 5 cm that do not regress or enlarge should be treated, but uncomplicated asymptomatic cysts less than 5 cm in diameter should only be observed and reassessed by serial ultrasonography. If they regress spontaneously, no surgical intervention is necessary independent of their sonographic findings.
Journal of Korean Medical Science 09/2006; 21(4):690-4. · 0.99 Impact Factor
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ABSTRACT: This study was undertaken to determine the clinical use of comparative genomic hybridization (CGH) for detection of fetal trisomy 21 from fetal ceIls (nucleated red blood cells; nRBCs) isolated from maternal peripheral venous blood.
Maternal peripheral venous blood samples were collected in sterile tubes containing heparin. After triple density gradient centrifugation, magnetic activated cell sorting using CD45 and CD71 was used to isolate the fetal nRBCs. Fetal nRBCs were successfully isolated from maternal peripheral blood in all cases. After laser-microdissecting fetal nRBCs, degenerate oligonucleotide-primed polymerase chain reaction, and nick translation, DNA size was suitable for hybridization.
By CGH analysis, we diagnosed one normal male, one normal female, and one trisomy 21 male fetus. These results were confirmed by amniocentesis.
Prenatal diagnosis from fetal cells in maternal peripheral blood by CGH shows clinical promise as an alternative or as a supplement to fluorescence in situ hybridization with chromosome-specific probes but further studies are warranted.
Fetal Diagnosis and Therapy 02/2006; 21(1):125-33. · 1.05 Impact Factor
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ABSTRACT: Adhesion molecules composed of Gly-Arg-Gly-Asp-Ser (GRGDS) peptides and cell recognition ligands were inculcated into thermo-reversible hydrogel composed of N-isopropylacrylamide, with a small amount of succinyl poly(ethylene glycol) (PEG) acrylate (MW 3400) used as a biomimetic extracellular matrix (ECM). The GRGDS-containing p(NiPAAm-co-PEG) copolymer gel was studied in vitro for its ability to promote cell spreading and to increase the viability of cells by introducing PEG spacers. Hydrogel lacking the adhesion molecules proved to be a poor ECM for adhesion, permitting only a 20% spread of the seeded cells after 10 days. When PEG spacer arms, immobilized by a peptide linkage, had been integrated into the hydrogel, conjugation of RGD promoted cell spread by 600% in a 10-day trial. In addition, in a serum-free medium, only GRGDS peptides conjugated with the spacer arm were able to promote cell spread. In terms of the cell viability, GRGDS peptides conjugated with the PEG-carrying copolymer gel specifically mediated cell spread. This result supports the theory that specific recognition is the result of interaction between the integrin families on the fibroblast, and the RGD sequence on the p(NiPAAm-co-PEG) copolymer gel.
Bioscience Biotechnology and Biochemistry 12/2004; 68(11):2224-9. · 1.28 Impact Factor
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ABSTRACT: This study was undertaken to establish a noninvasive prenatal genetic diagnostic method for trisomy 21 using the fetal nRBCs that is rarely present in maternal circulation. Peripheral venous blood samples were collected from 30 women with an advanced maternal age, abnormal triple marker test results, or abnormal ultrasound findings such as an increased nuchal translucency. The blood samples were treated with heparin. The triple density gradient centrifugation, and MACS using CD45 and CD71 were used to isolate the fetal cells. FISH analysis using probe 21 was performed with GPA-immunostaining. The study population consisted of 30 patients from 13 to 25 weeks of gestation, and nRBCs were separated in all cases. In GPA-immuno FISH analysis using probe 21, 3 cases of trisomy 21 were diagnosed and these results were confirmed by the amniocentesis. In conclusion, a prenatal diagnosis of trisomy 21 through GPA- immuno fluorescence in situ hybridization (FISH) analysis using separated fetal nRBCs is a useful, innovative, accurate, rapid and non-invasive diagnostic method.
Yonsei Medical Journal 05/2003; 44(2):181-6. · 1.14 Impact Factor
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ABSTRACT: Microdeletion of 22q11 is responsible for DiGeorge syndrome, velocardiofacial syndrome, congenital conotruncal heart defects, and related disorders. We report our experiences on prenatal diagnosis by fluorescence in situ hybridization (FISH) for 22q11 deletion in two fetuses with tetralogy of Fallot. Karyotyping and FISH of the parents revealed that one fetus inherited the disease from maternal microdeletion. These findings suggest the importance of performing FISH in pregnancies with prenatally detected tetralogy of Fallot.
Journal of Korean Medical Science 03/2002; 17(1):125-8. · 0.99 Impact Factor
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ABSTRACT: FastSLAM has been shown to degenerate over time due to sample impoverishment, that is, poor samples are generated during the sampling process. One of major culprits of the sample impoverishment problem is lack of the number of particles estimating the pose of the robot and the environment. In this work, an adaptive prior boosting technique is proposed for the efficient sample size according to the uncertainty of each situation in performing FastSLAM. It uses a back-propagation neural network, learned in various environments, in order to decide the required sample size. This adaptive approach generates a small number of particles when the uncertainty is low while performing FastSLAM, and it generates a large number of particles when the uncertainty is high. This technique efficiently generates the sample size in computer simulations and real environmental experiments, which significantly reduces the RMS feature and position errors.
Intelligent Robots and Systems, 2007. IROS 2007. IEEE/RSJ International Conference on;
