• Title/Summary/Keyword: BCR

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Apoptosis Induction in MV4-11 and K562 Human Leukemic Cells by Pereskia sacharosa (Cactaceae) Leaf Crude Extract

  • Asmaa, Mat Jusoh Siti;Al-Jamal, Hamid Ali Nagi;Ang, Cheng Yong;Asan, Jamaruddin Mat;Seeni, Azman;Johan, Muhammad Farid
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.475-481
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    • 2014
  • Background: Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia. Materials and Methods: Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. $IC_{50}$ concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting. Results: P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells. Conclusions: These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.

Coexisting JAK2V617F and CALR Exon 9 Mutations in Myeloproliferative Neoplasms - Do They Designate a New Subtype?

  • Ahmed, Rifat Zubair;Rashid, Munazza;Ahmed, Nuzhat;Nadeem, Muhammad;Shamsi, Tahir Sultan
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.923-926
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    • 2016
  • The classic BCR-ABL1-negative myeloproliferative neoplasm is an operational sub-category of MPNs that includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The JAK2V617F mutation is found in ~ 95% of PV and 50-60% of ET or PMF. In most of the remaining JAK2V617F-negative PV cases, JAK2 exon 12 mutations are present. Amongst the JAK2V617F-negative ET or PMF 5-10% of patients carry mutations in the MPL gene. Prior to 2013, there was no specific molecular marker described in the remaining 30-40% ET and PMF. In December 2013, two research groups independently reported mutations in the gene CALR found specifically in ET (67-71%) and PMF (56-88%) but not in PV. Initially CALR mutations were reported mutually exclusive with JAK2 or MPL. However, co-occurrence of CALR mutations with JAK2V617F has been reported recently in a few MPN cases. Many studies have reported important diagnostic and prognostic significance of CALR mutations in ET and PMF patients and CALR mutation screening has been proposed to be incorporated into WHO diagnostic criteria for MPN. It is suggestive in diagnostic workup of MPN that CALR mutations should not be studied in MPN patients who carry JAK2 or MPL mutations. However JAK2V617F and CALR positive patients might have a different phenotype and clinical course, distinct from the JAK2-positive or CALR-positive subgroups and identification of the true frequency of these patients may be an important factor for defining the prognosis, risk factors and outcomes for MPN patients.

The treatment of pediatric chronic myelogenous leukemia in the imatinib era

  • Lee, Jae-Wook;Chung, Nack-Gyun
    • Clinical and Experimental Pediatrics
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    • v.54 no.3
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    • pp.111-116
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    • 2011
  • Childhood chronic myelogenous leukemia (CML) is a rare hematologic disease, with limited literature on the methods of treatment. Previously, allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment for this disease. Treatment with imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase (TKI), has resulted in prolonged molecular response with limited drug toxicity. Imatinib is now implemented in the primary treatment regimen for children, but the paucity of evidence on its ability to result in permanent cure and the potential complications that may arise from long-term treatment with TKIs have prevented imatinib from superseding HSCT as the primary means of curative treatment in children. The results of allogeneic HSCT in children with CML are similar to those observed in adults; HSCT-related complications such as transplant-related mortality and graft-versus-host disease remain significant challenges. An overall consensus has been formed with regards to the need for HSCT in patients with imatinib resistance or those with advanced-phase disease. However, issues such as when to undertake HSCT in chronic-phase CML patients or how best to treat patients who have relapsed after HSCT are still controversial. The imatinib era calls for a reevaluation of the role of HSCT in the treatment of CML. Specific guidelines for the treatment of pediatric CML have not yet been formulated, underscoring the importance of prospective studies on issues such as duration of imatinib treatment, optimal timing of HSCT and the type of conditioning utilized, possible treatment pre-and post-HSCT, and the role of second-generation TKIs.

Fabrication and Evaluation Hydrogenation Absorbing on Mg2NiHx-10 wt% CaF2 Composites (Mg2NiHx-10wt% CaF2 수소저장합금의 제조와 수소화 흡수평가)

  • YU, JE-SEON;HAN, JUNG-HUM;SIN, HYO-WON;HONG, TAE-WHAN
    • Transactions of the Korean hydrogen and new energy society
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    • v.31 no.6
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    • pp.553-557
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    • 2020
  • It is possible that hydrogen could replace coal and petroleum as the predominant energy source in the near future, but several challenges including cost, efficiency, and stability. Mg and Mg alloys are attractive hydrogen storage materials because of their lightweight and high absorption capacity. Their range of applications could be further extended if their hydrogenation properties could be improved. The main emphasis of this study was to investigate their hydrogenation properties for Synthesis of 10wt.% CaF2 in Mg2NiHx systems. The effect of BCR (66:1) and MA time (96 hours) on the hydrogenation properties of the composite was investigated. also, Mg2NiHx-10wt% CaF2 composites prepared by Mechanical Alloying are used in this work to illustrate the effect of catalysts on activation energy and kinetics of Magnesium hydride.

Reinforcing Effect of Micropiles According to the Cohesive Characteristics of the Soil Layer Beneath Foundations (파일직경과 기초하부 토사층의 점착특성에 따른 마이크로파일 보강효과)

  • Jang, Chang-Hwan;Kim, Mu-Yeun;Hwang, Tae-Hyun
    • Journal of the Korean Geotechnical Society
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    • v.40 no.2
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    • pp.41-53
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    • 2024
  • Micropiles are small, cast-in-place piles with a diameter of 300 mm or less, primarily used to reinforce existing structures and support new constructions. As the application of these piles has expanded, extensive research has been conducted on their bearing characteristics, particularly in micropiled rafts. These studies have consistently demonstrated the positive impact of micropiles on foundation reinforcement. However, previous research often overlooked the potential variations in behavior between micropiled and conventional piled rafts based on different pile conditions. Furthermore, the influence of the cohesive characteristics of the soil layer beneath the foundation on the reinforcing effect of the micropiles has not been adequately addressed. This study, therefore, undertook 3D numerical analysis to assess the reinforcing effect of micropiles, considering both pile conditions and the cohesive characteristics of the soil layer beneath the foundation. The findings revealed that micropiles are significantly more effective in non-cohesive soil layers compared to cohesive ones, with the potential to increase the bearing capacity of the raft by up to 3.7 times.

Integrated Effect of Non-Invasive Neuromodulation on Bladder Capacity in Traumatic Spinal Cord Injury Patient: Single Case Report

  • Priyanka Dangi;Narkeesh Arumugam;Dinesh Suman
    • Physical Therapy Rehabilitation Science
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    • v.13 no.1
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    • pp.86-94
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    • 2024
  • Objective: To evaluate the changes in bladder capacity and storage through non-invasive neuromodulation by application of repetitive Trans magnetic stimulation (rTMS) and genital nerve stimulation (GNS) in traumatic spinal cord survivors. Design: A Single Case Study. Method: The Patient was registered in trail with the clinical trial registry of India (CTRI/2022/05/042431). The Patient was interposed with rTMS on lumbar area, from T11-L4 vertebrae with 1 Hz and the intensity was 20% below that elicited local paraspinal muscular contraction for 13 minutes. GNS was placed over dorsum of the penis with the cathode at the base and anode 2 cm distally at 20 Hz, 200 microseconds, Continuous and biphasic current was delivered and amplitude of stimulation necessary to elicit the genito-anal reflex. For assessment, Neurological examination was done for peri-anal sensation (PAS), voluntary anal contraction (VAC) and bulbocavernous reflex (BCR), deep anal pressure (DAP), and American Spinal Injury Association Impairment Scale (ASIA scale). Outcome assessment was done using Urodynamics, Spinal Cord Independence Measure Scale Version-III (SCIM-III), American Spinal Injury Association Impairment Score (ASIA Score), Beck's Depression Inventory Scale (BDI). The baseline evaluation was taken on Day 0 and on Day 30. Results: The pre-and post-data were collected through ASIA score, SCIM-III, BDI and Urodynamics test which showed significant improvement in bladder capacity and storage outcomes in the urodynamics study across the span of 4 weeks. Conclusion: rTMS along with GNS showed improvement in bladder capacity & storage, on sensory-motor score, in functional independence of individual after SCI.

A study of relationship between stomach cancer and selenoproteins in Korean human blood serum (한국인 혈청에서의 셀레노 단백질과 위암과의 상관관계 연구)

  • Park, Myungsun;Pak, Yong-Nam
    • Analytical Science and Technology
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    • v.28 no.6
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    • pp.417-424
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    • 2015
  • In this study, the relationship between selenoprotein concentrations in blood and stomach cancer have been searched for Korean. The concentration of each selenoprotein in blood serum was analyzed and the correlation between the concentration and stomach cancer was studied to find a potential for using Selenium as a biomarker. In concentration determination, a simple calibration curve method was used with the monitoring of m/z 78 without the use of solid phase extraction. This is a lot more simple than the method using SPE with post column isotope dilution. The result obtained from the analysis of CRM BCR-637, 72.20±3.35 ng·g−1, showed similar value of reference value (81±7 ng·g−1). The total concentration of Se for the controlled group, cardiovascular patients group, was 105.70±21.20 ng·g−1. This value was the same as normal healthy person reported earlier. Each selenoprotein concentration of GPx, SelP and SeAlb was 26.12±7.84, 65.15±14.50, 14.43±6.99 ng·g−1, respectively. The distribution of each selenoprotein was 24.7%, 61.6%, and 13.7%, which was similar to the normal person. The result of stomach cancer patients, the total concentration of Se was 76.11±28.12 ng·g−1 and each concentration of GPx, SelP and SeAlb was 15.41±9.01, 50.83±17.91, and 9.87±5.21 ng·g−1, respectively. The total and each selenoprotein concentration level showed significant decrease for the stomach cancer patients. The level of decrease was 41.0% for GPx, 22.0% for SelP, and 31.6% for SeAlb. However, the distribution of each selenoprotein was not much different. Either total Selenium or each selenoprotein could be used as a possible index for the diagnosis of cancer. However, in age group study, it is shown that young age group (30's-40's) did not show much difference.

Quantification of seleno proteins in Korean blood serum using solid phase extraction and affinity chromatography-inductively coupled plasma/mass spectrometry (고체상 추출과 친화 크로마토 그라피-유도결합 플라즈마 질량분석법을 이용한 한국인 혈청에서의 셀레노 단백질 정량)

  • Ahn, Ji-Yun;Kwon, Hyo-Sik;Pak, Yong-Nam
    • Analytical Science and Technology
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    • v.27 no.2
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    • pp.92-99
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    • 2014
  • Interferences were removed using anion exchange solid phase extraction (AE SPE) in quantification of selenoproteins in Korean human blood serum with affinity high performance liquid chromatography (AF HPLC)-inductively coupled plasma/mass spectrometry (ICP/MS). The average selenium level obtained for healthy Koreans was $94.3{\pm}2.3ngg^{-1}$ using isotope dilution method. AE SPE was coupled to AF column to separate 3 selenoproteins, glutathione peroxidase GPx, selenoprotein SelP, and selenoalbumin SeAlb. Post column isotope dilution was employed to quantify the proteins. The certified reference material of human blood serum BCR-637 was analyzed to give total selenoprotein concentration of $85.4{\pm}3.4ngg^{-1}$, which agreed well with the reference value of $81{\pm}7ngg^{-1}$. The pooled concentration of GPx, SelP, and SeAlb from healthy Koreans (n=20) was $12.1{\pm}1.4ngg^{-1}$, $57.2{\pm}2.0ngg^{-1}$, and $20.0{\pm}1.9ngg^{-1}$, respectively. The sum of selenoproteins is $89.3ngg^{-1}$, which is about the same as the total selenium concentration of $94.3ngg^{-1}$. The fact suggests that selenium in blood serum is mostly consisted of selenoproteins. After the removal of interference, GPx showed a significant decrease (more than 50%) from $25.0ngg^{-1}$ to $12.1ngg^{-1}$. It was identified that the interference in blood serum was mostly from GPx and the use of AE SPE was proven to be efficient in eliminating Cl and Br that cause interference to GPx.

Validation of Trienzyme Extraction-Microplate Assay for Folate in Korean Ancestral Rite Food (Trienzyme Extraction-Microplate Assay를 이용한 한국 차례 및 제사 음식의 엽산 분석 및 검증)

  • Park, Su-Jin;Jeong, Beom-Gyun;Jung, Jae Eun;Kim, Hyeon-Young;Jung, Gil-Rak;Hwang, Eun-Jung;Yoon, Sung-Won;Hyun, Taisun;Lee, Junsoo;Chun, Jiyeon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.5
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    • pp.716-724
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    • 2015
  • Trienzyme extraction coupled with microplate assay (Lactobacillus casei subsp. rhamnosus) was validated and applied for the determination of folate (vitamin B9) in Korean ancestral rite foods. Foods included five Guk (Tang), eleven Sookchaes, eight Jeoks, nine Jeons, six Jjims, and twenty desserts. Folate was detected in all samples: Guk (Tang) 4.62~18.84, Sookchae 6.13~48.40, Jeok 5.49~49.50, Jeon 6.96~30.77, Jjim 10.34~38.88, and desserts $3.33{\sim}49.55{\mu}g/100g$. The lowest folate content was observed in Sikhye ($3.33{\mu}g/100g$), whereas the highest was observed in Songhwa-dasik ($49.55{\mu}g/100g$). Folate analyses of certified reference materials, BCR-121 (whole meal flour) and BCR-487 (pig liver), showed good recoveries of 90.0% (0.45 mg/kg) and 92.4% (12.3 mg/kg), respectively. The recoveries (96.0 to 106.2%) obtained by analyzing eight spiked samples with different matrices also showed good accuracy. Both repeatability and reproducibility were less than 5%, indicating good precision. The quality control chart (n>30) obtained by running commercial folate fortified-wheat flour once a week for about 10 months showed that all assays were under control. All validation method and analytical quality control results showed that folate contents in Korean ancestral rite foods produced by microplate assay were reliable enough to be used for the construction of a national folate database.

Presence of Leukemia-maintaining Cells in Differentiation-resistant Fraction of K562 Chronic Myelogenous Leukemia (만성 골수성 백혈병 K562세포의 분화 내성 분획에서 백혈병 유지 세포의 동정)

  • Lee, Hong-Rae;Kim, Mi-Ju;Ha, Gahee;Kim, So-Jung;Kim, Sun-Hee;Kang, Chi-Dug
    • Journal of Life Science
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    • v.23 no.2
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    • pp.197-206
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    • 2013
  • The present study investigated whether leukemia-maintaining cells reside in a differentiation-resistant fraction using a megakaryocytic differentiation model of K562 cells. Treatment with phorbol-12-myristate-13-acetate (PMA) significantly inhibited the colony-forming efficiency of the K562 cells. At a PMA concentration of 1 nM or higher, colony was not formed, but approximately 40% of K562 cells still survived in soft agar. Approximately 70% of colony-forming cells that were isolated following the removal of PMA after exposure to the agent were differentiated after treatment with 10 nM PMA for 3 days. The differentiation rate of the colony-forming cells was gradually increased and reached about 90% 6 weeks after colony isolation, which was comparable to the level of a PMA-treated K562 control. Meanwhile, imatinib-resistant variants from the K562 cells, including K562/R1, K562/R2, and K562/R3 cells, did not show any colony-forming activity, and most imatinib-resistant variants were CD44 positive. After 4 months of culture in drug-free medium, the surface level of CD44 was decreased in comparison with primary imatinib-resistant variants, and a few colonies were formed from K562/R3 cells. In these cells, Bcr-Abl, which was lost in the imatinib-resistant variants, was re-expressed, and the original phenotypes of the K562 cells were partially recovered. These results suggest that leukemia-maintaining cells might reside in a differentiation-resistant population. Differentiation therapy to eliminate leukemia-maintaining cells could be a successful treatment for leukemia if the leukemia-maintaining cells were exposed to a differentiation inducer for a long time and at a high dose.