• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4857-4861
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• 2016

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R ($IC50=192{\mu}g/mL$) compared to K562 ($500{\mu}g/mL$) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5273-5278
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• 2015

Background: Chronic myeloid leukemia (CML) is a stem cell disorder characterized by the fusion of two oncogenes namely BCR and ABL with their aberrant expression. Autophosphorylation of BCR-ABL oncogenes results in proliferation of CML. The study deals with estimation of rate constant involved in each step of the cellular autophosphorylation process, which are consequently playing important roles in the proliferation of cancerous cells. Materials and Methods: A mathematical model was proposed for autophosphorylation of BCR-ABL oncogenes utilizing ordinary differential equations to enumerate the rate of change of each responsible system component. The major difficulty to model this process is the lack of experimental data, which are needed to estimate unknown model parameters. Initial concentration data of each substrate and product for BCR-ABL systems were collected from the reported literature. All parameters were optimized through time interval simulation using the fminsearch algorithm. Results: The rate of change versus time was estimated to indicate the role of each state variable that are crucial for the systems. The time wise change in concentration of substrate shows the convergence of each parameter in autophosphorylation process. Conclusions: The role of each constituent parameter and their relative time dependent variations in autophosphorylation process could be inferred.

• IMMUNE NETWORK
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• 제22권6호
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• pp.50.1-50.19
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• 2022

Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138^int B cells consisted of IgM^lowIgD^high follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138^int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138^int FO B cells was confirmed by attenuated Ca²⁺ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138^int FO B cells was distinct from that of the CD138^- FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca²⁺ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

• Ocean and Polar Research
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• 제36권4호
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• pp.343-351
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• 2014

The purpose of this study is to estimate the economic value and productivity achieved through a reduction in fishing vessels engaged in coastal and offshore fisheries. We found that the value of increasing catch by types in offshore and coastal fisheries was about 17,338 billion won. To examine the economic value, a cost-benefit analysis was applied. This is based on the total cost of vessel reduction (4,576 billion won) assumed to be invested equally each year for five years. BCR and NPV with a discount rate (5.5%) were used to compare the profit of fishery activities in offshore and coastal areas. The model results showed that the NPV and BCR in offshore and coastal fisheries was 5,522 billion won and 2.340 respectively.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2008년도 춘계학술발표대회
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• pp.1003-1006
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• 2008

인터넷상에서 TCP 프로토콜은 사실상 표준으로써 널리 이용되고 있다. 그러나 네트워크 환경이 발전해 감에 따라서 무선 네트워크, CDMA, 3G 네크워크등 다양한 환경이 공존하게 되었고, 이러한 환경에서 TCP의 성능저하가 이슈가 되어 많은 연구가 진행되었으며, 많은 알고리즘들이 발표되었다. 본 논문에서는 무선환경에서 다양한 TCP 성능저하 원인 중에서 spurious RTO에 관한 문제를 해결하고자 한다. 이 전의 연구인 E-RTO는 delay spike문제를 효과적으로 다루고 있다 하지만 delay spike이후 혼잡 윈도우를 회복하는 과정을 효과적으로 다루고 있지 못하다. 우리는 BCR를 제안하여 이러한 문제를 해결하고자 한다. BCR의 성능평가는 NS2를 이용하여 이루어 졌으며 throughput, goodput에서 좋은 성능을 보여주고 있다.

• 한국안광학회지
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• 제9권2호
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• pp.455-462
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• 2004

근시성 굴절이상자 85명 170안을 대상으로 구면 RGP렌즈를 피팅(Fitting)하여 RGP시험렌즈 BCR별, 각막난시량별, 각막의 만곡도별 누액렌즈굴절력 변화를 측정하여 분석한 결과 다음과 같은 결론을 얻었다. 1. RGP시럼렌즈 BCR의 변경에 의한 누액렌즈 굴절력은 "on-k"에서 -0.25D, 0.05Ft는 -0.46D, 0.10Ft는 -0.63D, 0.05St는 +0.07D, 0.10St는 +0.26D를 보였다. 2. 각막난시량별 RGP렌즈 BCR의 변경에 의한 누액렌즈 굴절력은 "on-k" 상태에서 각막난시 0.75D이하는 -0.25D, 1.00~1.25D는 -0.18D, 1.50~1.75D는 -0.09D, 2.00D이상에서는 -0.39D를 나타냈다. 3. 각막난시량별 시험렌즈 BCR을 0.05mm단계로 변경함에 따른 누액렌즈 굴절력의 변화량은 0.05St와 0.05Ft에서는 ${\pm}0.25D$에 근사한값을 나타냈지만 0.10St와 0.10Ft에서는 ${\pm}0.25D$이하의 불안정한 누액렌즈값을 나타냈다. 4. 각막의 만곡도별 RGP렌즈 BCR의 변경에 의한 누액렌즈 굴절력용 "on-k" 상태에서 7.50mm이하는 -0.40D, 7.55~7.80mm는 -0.11D, 7.85~8.20mm는 -0.20D, 8.25mm이상은 -0.19D를 나타냈다. 5. 각막만곡도별 시험렌즈 BCR을 0.05mm단계로 변경함에 따른 누액렌즈 굴절력의 변화량은 각막의 만곡도가 클수록 감소하는 경향을 보였으며 8.25mm이상은 평균 ${\pm}0.17D$로 ${\pm}0.25D$이하의 낮은 굴절력을 보였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4773-4780
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• 2014

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4555-4561
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• 2014

Background: Silencing due to methylation of suppressor of cytokine signaling-3 (SOCS-3), a negative regulator gene for the JAK/STAT signaling pathway has been reported to play important roles in leukemogenesis. Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein and induces hematological remission in patients with chronic myeloid leukemia (CML). Unfortunately, the majority of CML patients treated with imatinib develop resistance under prolonged therapy. We here investigated the methylation profile of SOCS-3 gene and its downstream effects in a BCR-ABL positive CML cells resistant to imatinib. Materials and Methods: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and $IC_{50}$ values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting. Results: The $IC_{50}$ for imatinib on K562 was 362nM compared to 3,952nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down-regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562. Conclusions: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.

• Journal of Yeungnam Medical Science
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• 제35권2호
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• pp.171-178
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• 2018

Background: To evaluate mid-term oncological and functional outcomes in patients with prostate cancer treated by robot-assisted laparoscopic radical prostatectomy (RALP) at our institution. Methods: We retrospectively reviewed the medical records of 128 patients with prostate cancer who underwent RALP at our institution between February 2008 and April 2010. All patients enrolled in this study were followed up for at least 5 years. We analyzed biochemical recurrence (BCR)-free survival using a Kaplan-Meier survival curve analysis and predictive factors for BCR using multivariate Cox regression analysis. Continence recovery rate, defined as no use of urinary pads, was also evaluated. Results: Based on the D'Amico risk classification, there were 30 low-risk patients (23.4%), 47 intermediaterisk patients (38.8%), and 51 high-risk patients (39.8%), preoperatively. Based on pathological findings, 50.0% of patients (64/128) showed non-organ confined disease (${\geq}T3a$) and 26.6% (34/128) had high grade disease (Gleason score ${\geq}8$). During a median follow-up period of 71 months (range, 66-78 months), the frequency of BCR was 33.6% (43/128) and the median BCR-free survival was 65.9 (0.4-88.0) months. Multivariate Cox regression analysis revealed that high grade disease (Gleason score ${\geq}8$) was an independent predictor for BCR (hazard ratio=4.180, 95% confidence interval=1.02-17.12, p=0.047). In addition, a majority of patients remained continent following the RALP procedure, without the need for additional intervention for post-prostatectomy incontinence. Conclusion: Our study demonstrated acceptable outcomes following an initial RALP procedure, despite 50% of the patients investigated demonstrating high-risk features associated with non-organ confined disease.

• 한국지반공학회:학술대회논문집
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• 한국지반공학회 1999년도 가을 학술발표회 논문집
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• pp.285-292
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• 1999

The cyclic plate load test were peformed to determine the behavior of reinforced soft ground with multiple layers of geogrid. Five series of test were conducted with varying the soil profile conditions which including the ground level, type of soil, and the thickness of each soil layer. The plate load test equipment was slightly modified to apply the cyclic load. Based on the cyclic plate load test results, the bearing capacity ratio(BCR), subbase modules, shear modules, the elastic rebound ratio, and reinforcing parameters are presented.