• Title/Summary/Keyword: AML (M3)

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Role of Krebs von den Lungen-6 (KL-6) in Assessing Hypersensitivity Pneumonitis

  • Mostafa, Amira Ismail;Salem, Ayman Elsayed;Ahmed, Heba Allah Moussa;Bayoumi, Aml Ibrahim;Halim, Radwa M. Abdel;Samie, Rasha M. Abdel
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.3
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    • pp.200-208
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    • 2021
  • Background: Hypersensitivity pneumonitis (HP) is an increasingly recognized form of diffuse parenchymal lung disease. Krebs von den Lungen-6 (KL-6) is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with interstitial lung diseases (ILD). Serum KL-6/MUC1 levels have been demonstrated to be useful for the evaluation of various ILD. To determine the role of circulating KL-6 in evaluating the disease activity and management of HP. Methods: An observational cross-sectional study was conducted on 51 patients with HP and 20 healthy controls. Serum KL-6 levels were measured in both groups. Patients were further assessed based on chest high-resolution computed tomography (HRCT), pulmonary function test, 6-minute walk test, echocardiography, bronchioalveolar lavage, and/or transbronchial biopsy. Patients were divided into the fibrotic and non-fibrotic groups according to the HRCT findings. Results: The median serum KL-6 levels were significantly higher in HP patients as compared to the control group. The median serum KL-6 levels were found to be higher in the non-fibrotic HP group (1,900 IU/mL) as compared to the fibrotic group (1,200 IU/mL). There was a significant inverse correlation between serum KL-6 serum level and the dose of steroids as well as the duration of steroid therapy. Conclusion: The presence of higher KL-6 levels in the non-fibrotic HP group implies its enhanced production by regenerating pneumocytes in response to alveolar injury. The significant association between serum KL-6 levels and the dose and the duration of steroid therapy emphasizes the significant role of steroids in the stabilization of the disease.

Estimation of Soil Loss Due to Cropland Increase in Hoeryeung, Northeast Korea (북한 회령지역의 농경지 변화에 따른 토양침식 추정)

  • Lee, Min-Boo;Kim, Nam-Shin;Kang, Chul-Sung;Shin, Keun-Ha;Choe, Han-Sung;Han, Uk
    • Journal of the Korean association of regional geographers
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    • v.9 no.3
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    • pp.373-384
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    • 2003
  • This study analyses the soil loss due to cropland increase in the Hoeryeung area of northeast Korea, using Landsat images of 1987 TM and 2001 ETM, together with DTED, soil and geological maps, and rainfall data of 20 years. Items of land cover and land use were categorized as cropland, settlement, forest, river zone, and sand deposit by supervised classification with spectral bands 1, 2 and 3. RUSLE model is used for estimation of soil loss, and AML language for calculation of soil loss volumes. Fourier transformation method is used for unification of the geographical grids between Landsat images and DTED. GTD was selected from 1:50,000 topographic map. Main sources of soil losses over 100 ton/year may be the river zone and settlement in the both times of 1987 and 2001, but the image of the 2001 shows that sources areas have developed up to the higher mountain slopes. In the cropland average, increases of hight and gradient are 24m and $0.8^{\circ}$ from 1987 to 2001. In the case of new developed cropland, average increases are 75m and $2.5^{\circ}$, and highest soil loss has occurred at the elevation between 300 and 500m. The soil loss 57 ton of 1987 year increased 85 ton of 2001 year. Soil loss is highest in $30{\sim}50^{\circ}$ slope zones in both years, but in 2001 year, soil loss increased under $30^{\circ}$ zones. The size of area over 200 ton/year, indicating higher risk of landslides, have increased from $28.6km^2$ of 1987 year to $48.8km^2$ of 2001 year.

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Synthetic Coprisin Analog Peptide, D-CopA3 has Antimicrobial Activity and Pro-Apoptotic Effects in Human Leukemia Cells

  • Kim, Soon-Ja;Kim, In-Woo;Kwon, Yong-Nam;Yun, Eun-Young;Hwang, Jae-Sam
    • Journal of Microbiology and Biotechnology
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    • v.22 no.2
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    • pp.264-269
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    • 2012
  • Recently, we reported that the synthetic Coprisin analog peptide 9-mer dimer CopA3 (consisted of all-L amino acid sequence) was designed based on a defensin-like peptide, Coprisin isolated from Copris tripartitus. The 9-mer dimer CopA3 (L-CopA3) had antibacterial activity and induced apoptosis in human leukemia cells via a caspase-independent pathway. In this study, all of amino acid sequences of L-CopA3 were modified to all D-form amino acids (DCopA3) to develop a more effective antimicrobial peptide. We investigated whether D-CopA3 had antimicrobial activities against pathogenic microorganisms and pro-apoptotic effects in human leukemia cells (U937, Jurkat, and AML-2). The synthetic peptide D-CopA3 had antimicrobial activities against various pathogenic bacteria and yeast fungus with MIC values in the 4~64 ${\mu}M$ range. Moreover, D-CopA3 caused cell growth inhibition, and increased the chromosomal DNA fragmentation and the expression of inflammatory cytokines, TNF-${\alpha}$ and IL1-${\beta}$, transcripts in human leukemia cells. The all-D amino acid peptide DCopA3 proved as effective as the L-CopA3 reported previously. These results provide the basis for developing D-CopA3 as a new antibiotic peptide.

Prognostic Value of a CYP2B6 Gene Polymorphism in Patients with Acute Myeloid Leukemia

  • Alazhary, Nevin M;Shafik, Roxan E;Shafik, Hanan E;Kamel, Mahmoud M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4583-4587
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    • 2015
  • Background: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. Materials and Methods: DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression-free survival (PFS) (p-value=0.245). Conclusions: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

Polyphenol Contents and Antioxidant Activities of Lentil Extracts from Different Cultivars (품종별 렌틸 추출물의 폴리페놀화합물 함량 및 항산화 활성)

  • Lee, So-Hee;Lee, Syng-Ook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.973-979
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    • 2016
  • Lentils (Lens culinaris) have been gaining increasing attention recently as a top five superfood, as they are high in protein and other essential nutrients, including folate, iron, potassium, and various antioxidants. In the present study, phenolic extracts from four different lentil cultivars (green, red, French, and beluga) were evaluated for their total phenolic contents and in vitro antioxidant activities. Total polyphenol and flavonoid contents of four different lentil extracts were 27.30~30.30 mg tannic acid equivalents (TAE)/g and 13.14~16.29 mg quercetin equivalents (QUE)/g, respectively. Beluga and red lentil extracts showed higher polyphenol contents than others (P<0.05), whereas there was no significant difference in flavonoid contents among the four lentil cultivars. $RC_{50}$ values of the lentil extracts for DPPH radical, ABTS radical, and $H_2O_2$ were $57.42{\sim}64.49{\mu}g/mL$, $66.11{\sim}75.69{\mu}g/mL$, and $59.72{\sim}72.86{\mu}g/mL$, respectively. Among the four lentil extracts, beluga lentil extract showed the most potent scavenging effect in all three reactive oxygen species (ROS) scavenging assays, and thus beluga extract was further tested for its inhibitory effect on early peroxidation of linoleic acid. The results showed that beluga lentil extract significantly inhibited linoleic acid peroxidation in a dose-dependent manner (concentration required for 50% reduction=$222.76{\m}g/mL$). In addition, beluga lentil extract showed a significant protective effect against alcohol-induced cytotoxicity in AML-12 cells (normal mouse hepatocyte cell line). Taken together, these results suggest that lentil extracts represent potential sources of natural antioxidants, and further studies will be necessary to determine their protective effects against oxidative stress in vivo.

In Vitro and In Vivo Effects of Piceatannol and Resveratrol on Glucose Control and TLR4-NF-κB Pathway (피세아테놀과 레스베라트롤의 혈당조절 및 TLR4-NF-κB 경로 조절 작용)

  • Lee, Hee Jae;Lee, Hae-Jeung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.2
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    • pp.267-272
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    • 2017
  • Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

Inhibitory Effect of Curcumin on MDR1 Gene Expression in Patient Leukemic Cells

  • Anuchapreeda, Songyot;Thanarattanakorn, Pattra;Sittipreechacharn, Somjai;Tima, Singkome;Chanarat, Prasit;Limtrakul, Pornngarm
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.866-873
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    • 2006
  • When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1 (MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of $10{\mu}M$ curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

THE EFFECT OF FIBROBLAST GROWTH FACTOR SIGNALING ON CARTILAGE FORMATION (FGF signaling이 연골 형성에 미치는 영향)

  • Park, Choong-Je;Lee, Sang-Won;Nam, Soon-Hyun;Kim, Young-Jin;Ryoo, Hyhn-Mo;Kim, Hyun-Jung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.4
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    • pp.643-653
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    • 2003
  • Fibroblast growth factor (FGF) / FGF receptor (FGFR) mediated signaling is required for skeletogenesis in cluding intramembranous and endochondral ossifications Runx2 ($Cbfa1/Pebp2{\alpha}A/AML3$) is an essential transcription factor for osteoblast differentiation and bone formation. Murine calvaria and mandible are concurrently undergoing both intramembranous bone and cartilage formations in the early developmental stage. However the mechanism by which these cartilage formations are regulated remains unclear. To elucidate the effect of FGF signaling on development of cranial sutural cartilage and Meckel's cartilage and to understand the role of Runx2 in these process, we have done both in vivo and in vitro experiments. Alcian blue staining showed that cartilage formation in sagittal suture begins from embryonic stage 16 (E16), Meckel's cartilage formation in mandible from E12. We analyzed by in situ hybridization the characteristics of cartilage cells that type II collagen, not type X collagen, was expressed in sagittal sutural cartilage and Meckel's cartilage. In addition, Runx2 was not expressed in Meckel's cartilage as well as sagittal sutural cartilage, except specific expression pattern only surrounding both cartilages. FGF signaling pathway was further examined in vitro. Beads soaked in FGF2 placed on the sagittal suture and mandible inhibited both sutural and Meckel's cartilage formations. We next examined whether Runx2 gene lies in FGF siganling pathway during regulation of cartilage formation. Beads soaked in FGF2 on sagittal suture induced Runx2 gene expression. These results suggest that FGF signaling inhibits formations of sagittal sutural and Meckel's cartilages, also propose that FGF siganling is involved in the proliferation and differentiation of chondroblasts through regulating the transcription factor Runx2.

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Second allogeneic hematopoietic stem cell transplantation in children to overcome graft failure or relapse after initial transplant (조혈모세포이식 후 생착 실패나 재발한 소아환자에서 2차 이식의 의의)

  • Kim, Dong-Yeon;Kim, Do Kyun;Kim, Soo Young;Kim, Seok Joo;Han, Dong Gyun;Baek, Hee Jo;Kook, Hoon;Hwang, Tai-Ju
    • Clinical and Experimental Pediatrics
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    • v.49 no.12
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    • pp.1329-1339
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    • 2006
  • Purpose : Failure of hematopoietic stem cell transplantation(HSCT) may be encountered in practice because of either relapse of the malignancy or dysfunction of the graft. Second HSCT may be the only option for some patients whose initial HSCT failed. Methods : From May, 1991 to December, 2004, 115 HSCTs were performed at the Pediatric Blood & Marrow Transplantation Center, Chonnam National University. This study was a retrospective analysis of the medical records of 15 patients who received the second HSCT after initial graft. Results : Among eight patients with nonmalignant diseases, two patients underwent the second HSCT because of primary graft failure and five because of late graft rejection. The remaining Fanconi anemia patient was re-transplanted due to development of AML. Two patients died and one experienced primary graft failure, but is still alive. The Kaplan-Meier 5-year overall survival rate was 75 percent and the disease free survival rate was 62.5 percent in nonmalignant diseases. All malignant patients underwent second transplants because of relapses. Four died of relapse and one of treatment-related complications. The Kaplan-Meier 2-year overall and event free survival rate was 28.6 percent each in malignant diseases. Conclusion : Second HSCT for graft dysfunction of nonmalignant disease seems to be feasible and should be considered as a standard practice. The relapse of malignant diseases remains a big obstacle even after the second HSCT, although a small portion of patients might be salvaged. Further investigation of novel therapeutic strategies, as well an the understanding of the biology should be explored.