• BMB Reports
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• 제56권2호
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• pp.78-83
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• 2023

Chronic myeloid leukemia (CML) has a markedly improved prognosis with the use of breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitors (BCR-ABL1 TKIs). However, approximately 40% of patients are resistant or intolerant to BCR-ABL1 TKIs. Hypoxia-inducible factor 1α (HIF-1α) is a hypoxia response factor that has been reported to be highly expressed in CML patients, making it a therapeutic target for BCR-ABL1 TKI-sensitive CML and BCR-ABL1 TKI-resistant CML. In this study, we examined whether HIF-1α inhibitors induce cell death in CML cells and BCR-ABL1 TKI-resistant CML cells. We found that echinomycin and PX-478 induced cell death in BCR-ABL1 TKIs sensitive and resistant CML cells at similar concentrations while the cell sensitivity was not affected with imatinib or dasatinib in BCR-ABL1 TKIs resistant CML cells. In addition, echinomycin and PX-478 inhibited the c-Jun N-terminal kinase (JNK), Akt, and extracellular-regulated protein kinase 1/2 (ERK1/2) activation via suppression of BCR-ABL1 and Met expression in BCR-ABL1 sensitive and resistant CML cells. Moreover, treatment with HIF-1α siRNA induced cell death by inhibiting BCR-ABL1 and Met expression and activation of JNK, Akt, and ERK1/2 in BCR-ABL1 TKIs sensitive and resistant CML cells. These results indicated that HIF-1α regulates BCR-ABL and Met expression and is involved in cell survival in CML cells, suggesting that HIF-1α inhibitors induce cell death in BCR-ABL1 TKIs sensitive and resistant CML cells and therefore HIF-1α inhibitors are potential candidates for CML treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9961-9966
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• 2014

Background: Some reports have suggested that chronic myeloid leukemia (CML) patients have a higher prevalence of M-bcr than acute lymphoblastic leukemia (ALL) patients, which show a higher prevalence of m-bcr. However, the relationship between BCR-ABL subtypes and progression of CML and ALL remains unclear. Materials and Methods: 354 CML chronic phase (CML-CP) patients, 26 CML blastic phase (CML-BP) patients and 72 ALL patients before treatment with BCR-ABL positive were recruited for blood routine examination and bone marrow smear cytology. Some 80 CML-CP and 32 ALL patients after imatinib (IM) treatment were followed-up for BCR-ABL relative concentrations detected after treatment for 3, 6 and 9 months and 1 year. Results: Before treatment, CML-CP patients showed lower BCR-ABL relative concentrations with a higher proportion of M-bcr (42.7%) compared to CML-BP and ALL patients while ALL patients had a higher BCR-ABL relative concentration with high expression of m-bcr (51.4%). Patients with M-bcr demonstrated higher WBC counts than those with m-bcr and the mixed group and higher PLT counts were noted in the CML-CP and ALL groups. After imatinib (IM) treatment, patients with m-bcr showed higher BCR-ABL relative concentrations in both CML-CP and ALL groups. Conclusions: This study identified the BCR-ABL gene as an important factor in CML and ALL cases. The M-bcr subtype was associated more with CML while the m-bcr subtype was associated more with ALL. Patients with m-bcr seem to have a poorer response to IM in either CML or ALL patients compared to M-bcr patients.

• Current Research on Agriculture and Life Sciences
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• 제7권
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• pp.67-71
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• 1989

Plate-Penetrometer를 사용(使用)하여 Gedtextile로 보강된 지반(地盤)의 지지력(支持力) 상승효과(上昇效果)를 고찰(考察)한 결과(結果) 다음과 같은 결론(結論)을 얻었다. 1. Geotextile의 포설층수(鋪設層數)를 3층(層)까지 증가(增加)하는 동안 BCR은 증가(增加)하였으나 그 이상(以上)의 포설층수(鋪設層數)에 대한 BCR의 증가효과(增加效果)는 거의 없는 것으로 나타났다. 2. U/D가 증가(增加)함에 따라 BCR은 감소(減少)하였으나 U/D가 0.8이상(以上)에서는 BCR의 변화(變化)가 거의 없는 것으로 나타났다. 3. ${\Delta}Z/D$가 0.6까지는 BCR이 급격(急激)히 감소(減少)하였으나 0.6이상(以上)에 대한 BCR의 감소율(減少率)은 거의 변화(變化)가 없는 것으로 나타났다. 4. Geotextile의 폭(幅)이 증가(增加)함에 따라 BCR은 거의 직선적(直線的)으로 증가(增加)하나 B/D가 2.5 이상(以上)에서는 증가율(增加率)이 현저(顯著)히 감소(減少)되는 것으로 나타났다.

• IMMUNE NETWORK
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• 제1권3호
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• pp.196-202
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• 2001

Backgorund: WEHI-231 B cell line is a representative model for $IgM^+$ mature B cells. To understand the signaling differences between mature and immature B cells, we compared the responsiveness of WEHI-231 and Bal 17 B cell lines to BCR cross-linking. Methods: The extents of tyrosine phosphorylation, ligand-induced internalization, and activation-induced cell death upon BCR cross-linking were compared in two cell lines. Results: Despite a higher expression of BCR, cross-linking of BCR on WEHI-231 cell evoked a weaker level of tyrosine phosphorylation and BCR endocytosis than Bal 17 cells. Furthermore, the endocytosed BCR could not enter the lysosomal compartment and stayed as peripheral spots in WEHI-231 cells. Conclusion: WEHI-231 cell showed preferred BCR-mediated signaling pathways leading to a reduced capability of antigen presentation as well as the enhanced apoptosis in comparision with Bal 17 cells. These results might reflect the signaling differences between mature and immature B cells.

• BMB Reports
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• 제29권3호
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• pp.241-247
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• 1996

The Philadelphia (Ph) chromosome is the single most intensively studied chromosome alteration characterizing a human malignancy. The specific genetic alteration of chronic myelogenous leukemia (CML) is the formation of the BCR/abl fusion gene in leukemic cells. The presence of the BCR/abl gene has important diagnostic and prognostic implications in CML. The detection of BCR/abl transcripts by reverse transcriptase based polymerase chain reaction (RT-PCR) was investigated in patients with CML in whom the Ph chromosome abnormality was documented by cytogenetic analysis. In a total of 68 CML patient cases, the Ph chromosome was found in 53 cases (77.9%) by cytogenetic analysis. On the other hand, sixty two cases (91.2%) were detected to have BCR/abl gene rearrangement Of these, b3a2 was 44 cases (64.7%) and b2a2 was 17 cases (25,0%). There was one case with both b3a2 and b2a2 (1.5%). Of the fifteen cases of Ph chromosome negative by cytogenetic anlaysis, the BCR/abl gene was observed in nine cases, The results of BCR/abl fusion gene confirmed by the direct sequencing method correlated well with PCR analysis, The amplified PCR products were detected by $1{\times}10^{-5}$ dilutions. In conclusion, PCR technique is sensitive, rapid and relatively simple for a laboratory test in detecting the BCR/abl fusion gene with CML regardless of the result of cytogenetic analysis.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.179-187
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• 2011

Regulation of B cell receptor (BCR)-induced $Ca^{2+}$ signaling by CD40 co-stimulation was compared in long-term BCR-stimulated immature (WEHI-231) and mature (Bal-17) B cells. In response to long-term pre-stimulation of immature WEHI-231 cells to ${\alpha}$-IgM antibody (0.5~48 hr), the initial transient decrease in BCR-induced $[Ca^{2+}]_i$ was followed by spontaneous recovery to control level within 24 hr. The recovery of $Ca^{2+}$ signaling in WEHI-231 cells was not due to restoration of internalized receptor but instead to an increase in the levels of $PLC{\gamma}2$ and $IP_3R-3$. CD40 co-stimulation of WEHI-231 cells prevented BCR-induced cell cycle arrest and apoptosis, and it strongly inhibited the recovery of BCR-induced $Ca^{2+}$ signaling. CD40 co-stimulation also enhanced BCR internalization and reduced expression of $PLC{\gamma}2$ and $IP_3R-3$. Pre-treatment of WEHI-231 cells with the antioxidant N-acetyl-L-cysteine (NAC) strongly inhibited CD40-mediated prevention of the recovery of $Ca^{2+}$ signaling. In contrast to immature WEHI-231 cells, identical long-term ${\alpha}$-IgM pre-stimulation of mature Bal-17 cells abolished the increase in BCR-induced $[Ca^{2+}]_i$, regardless of CD40 co-stimulation. These results suggest that CD40-mediated signaling prevents antigen-induced cell cycle arrest and apoptosis of immature B cells through inhibition of sustained BCR-induced $Ca^{2+}$ signaling.

• 한국산학기술학회논문지
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• 제14권3호
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• pp.1258-1265
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• 2013

본 논문의 목적은 랩탑 컴퓨터의 터치패드 및 두 개의 클릭 버튼 위치에 따른 손목과 어깨 부위 근육의 EMG 진폭 및 중앙 주파수 변화를 알아보는 것이다. 기존 연구결과를 바탕으로 손목과 어깨의 외전현상이 근골격계질환으로 이어지는 메커니즘을 살펴보고, 이를 토대로 연구가설이 설정되었다. 실험에서 터치패드 및 클릭버튼의 위치는 기존의 중앙 아래(bottom center, BC)와 중앙 아래에 위치하지만 $45^{\circ}$ 반시계방향으로 회전된 방식(bottom center with rotation, BCR), 그리고 회전없이 중앙 오른쪽에 위치한 경우(bottom right, BR)가 비교되었다. 10명의 피실험자는 오른 손으로 5분 동안 터치패드 및 두 개의 버튼을 이용하는 task를 각각의 시행하는 동안 EMG 진폭과 중앙 주파수가 측정되었다. 손목 부위의 근육은 척측수근굴근, 어깨부위의 근육은 위쪽 승모근이 선정되었다. 실험결과 손목부위에서는 BC의 경우가 진폭은 크게 나타나고 중앙 주파수는 작게 나타났으며, 어깨부위에서는 BC와 BCR이 BR보다 진폭은 크고 중앙 주파수는 작게 나타났다. 또한, 손목부위에서는 진폭과 중앙 주파수 모두에서 BCR과 BR의 차이가 유의하게 나타나지 않았고, 어깨부위에서는 BC와 BCR에서의 차이가 나타나지 않았다. 이러한 결과는 BC에서는 손목과 어깨의 외전이 동시에 나타나고, BCR은 어깨의 외전만, 그리고 BR은 손목과 어깨에서 외전이 모두 나타나지 않기 때문이다.

• 콘크리트학회논문집
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• 제24권4호
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• pp.445-452
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• 2012

이 연구에서는 기존 철근콘크리트 건축물의 구조성능 향상을 위하여 매입형 FRP봉과 보강철물을 보강한 철근콘크리트 보의 구조성능을 평가하기 위하여 실험을 수행하였다. 매입형 FRP봉의 사용량, 보강철물 유무에 따라 총 7개의 실험체를 제작하고 실험을 수행하여 구조성능을 평가하였으며, 이 연구의 실험 결과를 근거로 다음과 같은 결론을 얻었다. 매입형 FRP봉 보강실험체(BCR 시리즈)의 경우 표준실험체(BSS)와 비교하여 21~55% 내력이 증가하였고, 매입형 FRP봉과 보강철물을 보강한 실험체(BCR-AC 시리즈)는 표준실험체(BSS)보다 최대내력이 21~63% 증가하였다. 그리고 매입형 FRP봉으로 보강된 실험체는 부착슬립, 피복분리 형태로 파괴되었으나, 매입형 FRP봉과 보강철물을 보강한 실험체는 보강철물의 구속효과로 부착슬립의 형태로 파괴되었다.

• 한국환경보건학회지
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• 제23권1호
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• pp.74-80
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• 1997

This study was performed to estimate the ozonation characteristics of phenol wastewater with increasing pH in the continuous packed column reactor (PCR) and the bubble column reactor (BCR). Among various influencing factors that affect phenol on decomposition through the ozonation, pH was chosen as reaction parameter. Upon increasing pH from 3 to 9, the phenol removal efficiency in PCR was improved approximately by 17% while in BCR approximately by 19.2%. The improvements in the phenol removal efficiency by increasing pH caused the enhancements in ozone utilization efficiency reaching almost 100% in PCR at pH 9. In conclusions, ozone has latent power for phenol wastewater treatment, and the performance of PCR was superior to that of BCR in the aspects of phenol removal and ozone utilization efficiency.

• 한국환경보건학회지
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• 제21권2호
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• pp.12-19
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• 1995

The objectives of this research prograln were to study the ozonation characteristics of phenol contaminated wastewater in the continuous packed column reactor (PCR) and the bubble column reactor (BCR) using ozone that has a strong oxidizing potential, and to provide the fundamentals of ozonizing the phenol contaminated wastewater. Among various influencing factors on phenol decomposition through the oxidation by ozone, phenol/ozone mde ratio was chosen as reaction parameters. Concerning the phenol/ozone mde ratio, as the influent phenol concentration increased from 30 mg/l to 150 mg/l, the phenol removal efficiency decreased from 99% for 30 mg/l to 83.7% for 150 mg/l, in PCR. PCR also showed higher treatment efficiency than BCR by 1% for 30 mg/l and 2.2% for 150 mg/l, respectively. The ozone utilization efficiency of PCR for the phenol concentration 30 mg/l was higher than that of BCR while the efficiency of both reactors was 99.9% for the phenol concentration of 150 mg/l.