• Title/Summary/Keyword: K-Ras

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A Comparison of ROCK Inhibitors on Human Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Neuron-Like Cells

  • Lee, Hyun-Sun;Kim, Kwang-Sei;O, Eun-Ju;Joe, Young-Ae
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.386-395
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    • 2010
  • Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and $CoCl_2$. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of $CoCl_2$. Y27632 with high specificity for ROCK at 1-30 ${\mu}M$ was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100 ${\mu}M$, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including ${\beta}$-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.

Enhancement of Digital Elevation Models for Improved Estimation of Small Stream Flood Inundation Mapping (DEM 개선을 통한 중소하천 홍수범람지도 정확도 향상)

  • Kim, Tae-Eun;Seo, Kang-Hyeon;Kim, Dong-Su;Kim, Seo-Jun
    • Journal of Environmental Science International
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    • v.25 no.8
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    • pp.1165-1176
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    • 2016
  • The accuracy of digital elevation models (DEMs) is crucial for properly estimating flood inundation area. DEM pixel size is especially important when generating flood inundation maps of small streams with a channel width of less than 50 m. In Korea, DEMs with large spatial resolutions of 30 m have been widely applied to generate flood inundation maps, even for small streams. Additionally, when making river master plans, field observations of stream cross-sections, as well as reference points in the middle of the river, have not previously been used to enhance the DEM. In this study, it was graphically demonstrated that high-resolution DEMs can increase the accuracy of flood inundation mapping, especially for small streams. Also, a methodology was proposed to modify the existing low-resolution DEMs by adding additional survey reference points, including river cross-sections, and interpolating them into a high spatial resolution DEM using the inverse distance weighting method. For verification purposes, the modified DEM was applied to Han stream on Jeju Island. The modified DEM showed much better accuracy when describing morphological features near the stream. Moreover, the flood inundation maps were formulated with the original 30 m pixel DEM and the modified 0.1 m pixel DEM using HEC-RAS modeling of the actual flood event of Typhoon Nari, and then compared with the flood history map of Nari. The results clearly indicated that the modified DEM generated a similar inundation area, but a very poor estimate of inundation area was derived from the original low-resolution DEM.

Differential Gene Expression in Estradiol-3-Benzoate-Treated Liver and Chemically- Induced Hepatocellular Carcinoma

  • KIM , SEYL;KANG, JIN-SEOK;JANG, DONG-DEUK;LEE, KOOK-KYUNG;KIM, SOON-AE;HAN, BEOM-SEOK;PARK, YOUNG-IN
    • Journal of Microbiology and Biotechnology
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    • v.14 no.6
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    • pp.1286-1294
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    • 2004
  • In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

Spinal Cord Ependymoma Associated with Neurofibromatosis 1 : Case Report and Review of the Literature

  • Cheng, Hongwei;Shan, Ming;Feng, Chunguo;Wang, Xiaojie
    • Journal of Korean Neurosurgical Society
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    • v.55 no.1
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    • pp.43-47
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    • 2014
  • Patients with neurofibromatosis 1 (NF1) are predisposed to develop central nervous system tumors, due to the loss of neurofibromin, an inactivator of proto-oncogene Ras. However, to our knowledge, only three cases of ependymomas with NF1 have been reported in the literature. The authors present a case of NF1 patient with a spinal cord ependymoma. She was referred for about half a year history of increasing numbness that progressed from her fingers to her entire body above the bellybutton. Magnetic resonance imaging revealed a relative-demarcated, heterogeneously enhanced mass lesion accompanied by perifocal edema in C5-7 level, a left-sided T11 spinous process heterogeneously enhanced mass in soft tissue, intervertebral disk hernia in L2-5 level, and widespread punctum enhancing lesion in her scalp and in T11-L5 level. The patient underwent C5-7 laminectomies and total excision of the tumor under operative microscope, and intraoperative ultrasonography and physiological monitoring were used during the surgery. Histopathologically, her tumor was found to be a ependymoma without malignant features (grade II in the World Health Organization classification). Therefore, no adjuvant therapy was applied. Following the operation, the patient showed an uneventful clinical recovery with no evidence of tumor recurrence after one year of follow-up.

Treatment of Vemurafenib-Resistant SKMEL-28 Melanoma Cells with Paclitaxel

  • Nguyen, Dinh Thang;Phan, Tuan Nghia;Kumasaka, Mayuko Y.;Yajima, Ichiro;Kato, Masashi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.699-705
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    • 2015
  • Vemurafenib has recently been used as drug for treatment of melanomas with $BRAF^{V600E}$ mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant $BRAF^{V600E}$ melanoma cell lines, $A375P^R$, $A375M^R$ and SKMEL-$28^R$, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-$28^R$ cells. Treatment of SKMEL-$28^R$ cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-$28^R$ were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of $BRAF^{V600E}$-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.

Does Beta-blocker Therapy Improve the Survival of Patients with Metastatic Non-small Cell Lung Cancer?

  • Aydiner, Adnan;Ciftci, Rumeysa;Karabulut, Senem;Kilic, Leyla
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6109-6114
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    • 2013
  • Aim: To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. Results: The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (${\pm}2.87$) months (95%CI: 13.62-24.88) in the BB group and 13.20 (${\pm}2.37$) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. Conclusions: The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.

The Method of MBS Data Transmission Synchronization Using Loss Preventive Device of Transmission Synchronization Information and Its Packet Data (전송 동기화 정보와 패킷 데이터 손실 방지 장치를 이용한 멀티캐스트/브로드캐스트 서비스 데이터 전송 동기화 방법)

  • Kim, Kwang-Yong;Kim, Young-Il;Cho, Cheol-Hoe;Ryu, Won
    • Proceedings of the Korean Society of Broadcast Engineers Conference
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    • 2011.11a
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    • pp.251-254
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    • 2011
  • 와이브로(Wibro) 또는 WiFI 망에서 동일한 멀티캐스트 그룹에 속한 이동 단말기들은 동일한 MBS(멀티캐스트/브로드캐스트 방송 서비스) 콘텐츠를 수신한다. 동일한 MBS 존 내의 기지국(RAS: Radio Access Station) 들이 MBS 콘텐츠 소스로부터 수신된 MBS 콘텐츠에 대한 전송 시간을 동기화할 수 있도록 기지국들은 전송 동기화 정보와 신뢰성 있는 데이터 패킷 수신을 동기 시간을 결정하기 이전에 보장받을 수 있어야 한다. 만약에 동일한 MBS 존에 속하는 다수의 기지국 중에 전송 동기화 정보를 수신하지 못하거나 패킷 데이터 일부 또는 전부를 수신하지 못한다면, 동기 전송 시간을 결정하기 전에 이미 손실된 정보와 패킷 데이터를 이동 단말기로 전송하게 됨으로써 이동 단말기가 MBS 콘텐츠를 수신하면서 동일 MBS 존 내의 다른 기지국으로 핸드오버하게 되면 MBS 콘텐츠에 대한 끊김없는 수신을 보장할 수 없을 뿐만 아니라 매크로 다이버시티(macro diversity) 이득을 얻기 위한 동일한 MBS 존에서 이동 단말기들에게 전송되는 MBS 콘텐츠들의 동기를 보장 할 수 없다. 따라서, 본 논문에서는 동기 전송 시간을 결정하기 앞서서 다수의 RAS가 전송 동기화 정보와 신뢰성 있는 패킷 데이터 콘텐츠 수신을 보장받을 수 있는 장치를 보완한 멀티캐스트/브로드캐스트 서비스 데이터 전송 동기화 방법을 제안한다.

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Protein Carboxyl Ο-Methylation in Porcine Liver and Testis (돼지 간 및 정소에서 단백질 카르복실메칠화 현상)

  • 조재열;김성수;이향우;홍성렬
    • YAKHAK HOEJI
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    • v.45 no.1
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    • pp.46-54
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    • 2001
  • Protein carboxyl Ο-methylation is a kind of enzymatic reaction producing carboxyl methylester catalyzed by protein carboxyl Ο-methyltransferases at the carboxyl group of amino acid residues in polypeptide. Since the finding of carboxyl methylesterl many studies have been focused on the under-standing of biological functions in eukaryotes but still not clear except for roles in Ras attachment to membrane and protein repair. In this study, we investigated the protein carboxyl methylation in porcine liver and testis in respect of identification and characterization of carboxyl methylesters and natural proteinous substrates using pH stability of the esters and electrophoresis under acidic and basic conditions. We detected several kinds of methyl esters, 3 kinds each in cytosolic fractions from liver and testis. Under the treatment of strong acid and base, the ratio between base-stable substrates and unstable ones in liver (4 : 6) was different from the ratio obtained in testis (6 : 4). The methyl accepting capacities were affected by enzymatic proteolysis between the range of 55 to 65% in liver and of 35 to 45% in testis. Separation of the methylated proteins by acidic electrophoresis in the presence of urea and SDS revealed distinctively natural substrates of 26, 33 and 80 kD in the cytosol from liver and of 14, 25, 32 and 86 kD from testis. Most of the labelling, however were lost following electrophoresis under moderate alkaline condition, except for molecules of newly detected 7 and 17 kD in livers and 15, 29, 40 and 80 kD in testis. From these results, it was proposed that protein carboxyl Ο-methylation in each organs may be catalyzed by different classes of protein carboxyl Ο-methyltransferases. In addition, it is suggested that the protein carboxyl methylation in liver and testis may have different patterns in respect of natural substrates.

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Friable Test and Risk Assessment for Asbestos in Soils using the Releasable Asbestos Sampler (RAS) (석면 비산 장비를 이용한 토양 중 석면 비산 특성 및 위해성 평가)

  • Kim, In Ja;Kim, Jeong-Wook;Ryu, Hyun Sik;Jung, Myung Chae
    • Journal of Soil and Groundwater Environment
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    • v.17 no.5
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    • pp.68-74
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    • 2012
  • The objective of this study is to examine a releasable asbestos sampler developed for measuring friable asbestos from soil to air controlled by wind velocity and water contents. Asbestos contaminated soil with 3.75% at the Sinsuk-asbestos mine was sampled, air-dried and sieved to 100 mesh, then homogenized during 24 hours' agitation. Various wind velocities, 1 m/s, 2 m/s, 3 m/s, and 5 m/s, were applied to evaluate releasable characteristics of the releasable asbestos sampler. In addition, soils with 1.0%, 3.4%, 4.4%, 11.0%, 16.2%, and 20.0% of water contents were also examined the amount of friable asbestos by the releasable asbestos sampler. Collected soil and air samples were analyzed by polarized light microscopy (PLM) and phase contrast microscopy (PCM), respectively. Those contents were applied to calculate an excess life cancer risk (ELCR). This study also discussed the relationship with risk assessment by a weeding scenario of activity based sampling (ABS) and field applied releasable asbestos sampler. The result was shown that friability of asbestos in soil increased with wind velocity and decreased with water content. In comparison with ELCR results, over 10E-4 of cancer risk was found in condition on < 5% water content and > 3m/s wind velocity.

Sex-related Clinicopathologic Differences in Patients with Adenocarcinoma of the Lung (성별에 따른 원발성 폐선암 환자들의 차이)

  • Park, Eun Ho;Jang, Tae Won;Jang, Li La;Paek, Jong yun;Oak, Chul Ho;Jung, Mann Hong;Jang, Hee Kyung
    • Tuberculosis and Respiratory Diseases
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    • v.62 no.3
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    • pp.203-210
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    • 2007
  • Background: The incidence of adenocarcinoma of the lung has been increasing worldwide, and it has been generally been accepted to be relatively unrelated to smoking with a female preponderance. The aim of this study was to examine the gender-related pathological and survival differences in patients with an adenocarcinoma of the lung. Material and Method: A retrospective review of the clinical information of patients diagnosed with an adenocarcinoma of the lung at Kosin Medical Center from January 1999 to September 2005 was performed. The patient's demographics (age, gender), smoking history, stage, serum tumor marker, pathology classification, EGFR mutation, K-ras mutation, treatment methods, and survival time were analyzed. Result: Of the 438 patients, 179 (40.9%) were female. The median age at the diagnosis was 58 years for females and 59 years for males. However, 25.8% of women and only 17.7% of men were under 50 years of age (p=0.02). The distribution of the disease stage was similar in both men and women. The bronchioloalveolar carcinoma component was diagnosed more often in women (11.2%) than in men (5.0%). The overall survival rate was higher in women than in men (p=0.01), and women had a superior therapeutic response to a combined treatment of surgery and chemotherapy. Conclusion: This study showed significant genders differences in terms of the smoking history, bronchioloalveolar carcinoma component, overall survival, and survival after combined treatment of surgery and chemotherapy. Therefore, gender differences should be considered when diagnosing and treating adenocarcinomas of the lung.