• BMB Reports
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• v.56 no.2
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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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• v.15 no.22
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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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• v.7
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• pp.67-71
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• 1989

To consider improvement effect of the bearing capacity and economical efficiency in using the geotextile, on foundation reinforced with the geotextile, several experiments accomplished by the plate-penetrometer on a model foundation. The results obtained are as follows : 1. It appears that the BCR is increased steeply only to 3 layers of the geotextile but nearly isn't more than 3 layers. 2. It appears that the BCR is increased during the U/D's increment but the variations of it nearly isn't more than U/D=0.8. 3. It appears that the BCR is increased steeply to the value of ${\Delta}Z/D$=0.6 but variations of it nearly isn't more than 0.6. 4. It appears that the BCR is decreased almost proportionally to the value of B/D= 2.5 but it's ratio of decrease is decreased remarkably more than 2.5.

• IMMUNE NETWORK
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• v.1 no.3
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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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• v.29 no.3
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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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• v.15 no.3
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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.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.14 no.3
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• pp.1258-1265
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• 2013

The objective of this study is to investigate the association between touchpad &buttons locations in a laptop computer and EMG amplitude and median frequency in muscles related with wrist and shoulder. Based on previous studies it was shown how abductions in wrist and shoulder could cause musculoskeletal disorders in those body parts, on which research hypotheses were established. Touchpad &buttons positions consisted of bottom center(BC), bottom center with $45^{\circ}$ rotation counterclockwise(BCR), and bottom right(BR). 10 subjects performed the task that required only touchpad &buttons usage with their preferred hand and EMG amplitude and median frequency data were recorded during 5min and analyzed afterwards. Upper trapezius and flexor carpi ulnaris were selected as target muscles. The results showed that in flexor carpi ulnaris BC resulted in greater amplitude and less median frequency than BCR and BR, but there was no significant difference between BCR and BR. In upper trapezius BC and BCR induced higher amplitude and lower median frequency than BR, but the significant difference between BC and BCR was not observed. Those phenomena occurred since BC gave rise to both wrist and shoulder abduction, BCR caused only shoulder one, and BR did not lead to abductions in both wrist and shoulder.

• Journal of the Korea Concrete Institute
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• v.24 no.4
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• pp.445-452
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• 2012

In this study, experimental research was carried out to evaluate the structural performance of the reinforced concrete beam using strengthening materials (embedded FRP rod, metal fittings) in existing reinforced concrete buildings. Seven reinforced concrete beams comprised of retrofitted embedded FRP rod (BCR series), embedded FRP rod with metal fittings (BCR-AC series), and standard specimen (BSS) were constructed and tested under monotonic loading. Design parameters of test specimens were amount of embedded FRP rod and metal fittings. The test results showed that the maximum load carrying capacity of specimens with embedded FRP rod (BCR series) and embedded FRP rod with metal fittings (BCR-AC series) increased by 21~55% and 21~63%, respectively, in comparison with the standard specimen BSS. BCR series test specimens failed by the adhesion slip and concrete cover separation. BCR-AC series test specimens failed by the adhesion slip due to the confining effect of metal fittings.

• Journal of Environmental Health Sciences
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• v.23 no.1
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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.

• Journal of Environmental Health Sciences
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• v.21 no.2
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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.