• Title/Summary/Keyword: Lymphoblastic

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Classification of Leukemia Disease in Peripheral Blood Cell Images Using Convolutional Neural Network

  • Tran, Thanh;Park, Jin-Hyuk;Kwon, Oh-Heum;Moon, Kwang-Seok;Lee, Suk-Hwan;Kwon, Ki-Ryong
    • Journal of Korea Multimedia Society
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    • v.21 no.10
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    • pp.1150-1161
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    • 2018
  • Classification is widely used in medical images to categorize patients and non-patients. However, conventional classification requires a complex procedure, including some rigid steps such as pre-processing, segmentation, feature extraction, detection, and classification. In this paper, we propose a novel convolutional neural network (CNN), called LeukemiaNet, to specifically classify two different types of leukemia, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and non-cancerous patients. To extend the limited dataset, a PCA color augmentation process is utilized before images are input into the LeukemiaNet. This augmentation method enhances the accuracy of our proposed CNN architecture from 96.9% to 97.2% for distinguishing ALL, AML, and normal cell images.

Study of Signaling Pathway on Apoptotic Cell Death Induced by Extract of Ailanthus altissima in Human Jurkat Lymphocytes (저근백피(樗根白皮) 추출물에 의한 급성 림프성 백혈병 Jurkat Lymphocytes의 세포고사 유도 및 신호기전 연구)

  • Lee, Ki Ouk;Kim, Ae Wha;Lim, Kyu Sang;Yun, Young Gab
    • Herbal Formula Science
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    • v.25 no.3
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    • pp.349-362
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    • 2017
  • Objectives : We investigated whether the components of Ailanthus altissima induced apoptotic cell death in Jurkat acute lymphoblastic leukemia (ALL) cells. Methods : Regulation of cell proliferation is a complex process involving the regulated expression and/or modification of discrete gene products, which control transition between different stages of the cell cycle. Results : Upon treatments with Ailanthus altissima, the concentration-dependent inhibitions of cell viability were observed as compared to untreated control group. The capability of Ailanthus altissima to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly(ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Ailanthus altissima also caused apoptosis as measured by cell morphology and DNA fragmentation. Conclusions : These results indicate that the increase of apoptotic cell death by Ailanthus altissima may be due to the inhibition of cell cycle in human Jurkat lymphocytes. Conclusively, these current and further findings will provide novel approaches to understanding and treating major diseases.

Curcumin Induces Apoptosis in Pre-B Acute Lymphoblastic Leukemia Cell Lines Via PARP-1 Cleavage

  • Mishra, Deepshikha;Singh, Sunita;Narayan, Gopeshwar
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3865-3869
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    • 2016
  • Curcumin, a polyphenolic compound isolated from the rhizomes of an herbaceous perennial plant, Curcuma longa, is known to possess anticancerous activity. However, the mechanism of apoptosis induction in cancers differs. In this study, we have (1) investigated the anticancerous activity of curcumin on REH and RS4;11 leukemia cells and (2) studied the chemo-sensitizing potential of curcumin for doxorubicin, a drug presently used for leukemia treatment. It was found that curcumin induced a dose dependent decrease in cell viability because of apoptosis induction as visualized by annexin V-FITC/ PI staining. Curcumin-induced apoptosis of leukemia cells was mediated by PARP-1 cleavage. An increased level of caspase-3, apoptosis inducing factor (AIF), cleaved PARP-1 and decreased level of Bcl2 was observed in leukemia cells after 24h of curcumin treatment. In addition, curcumin at doses lower than the $IC_{50}$ value significantly enhanced doxorubicin induced cell death. Therefore, we conclude that curcumin induces apoptosis in leukemia cells via PARP-1 mediated caspase-3 dependent pathway and further may act as a potential chemo-sensitizing agent for doxorubicin. Our study highlights the chemo-preventive and chemo-sensitizing role of curcumin.

Synthesis and Biological Evaluation of Tetrapeptide Ketones as Reversible 20S Proteasome Inhibitors

  • Latif, Muhammad;Jung, Myoung Eun;Lee, Kwangho;Choi, Gildon
    • Bulletin of the Korean Chemical Society
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    • v.35 no.12
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    • pp.3571-3575
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    • 2014
  • Proteasome, a multicatalytic protease complex, has been validated as a promising therapeutic target in oncology. Carfilzomib (Kyprolis$^{(R)}$), a tetrapeptide epoxyketone, irreversibly inhibits the chymotrypsin-like (CT-L) activity of the proteasome and has been recently approved for multiple myeloma treatment by FDA. A chemistry effort was initiated to discover the compounds that are reversibly inhibit the proteasome by replacing the epoxyketone moiety of carfilzomib with a variety of ketones as reversible and covalent warheads at the C-terminus. The newly synthesized compounds exhibited significant inhibitory activity against CT-L activity of the human 20S proteasome. When the compounds were tested for cancer cell viability, 14-8 was found to be most potent in inhibiting Molt-4 acute lymphoblastic leukemia cell line with a $GI_{50}$ of $4.4{\mu}M$. Cytotoxic effects of 14-8 were further evaluated by cell cycle analysis and Western blotting, demonstrating activation of apoptotic pathways.

Houttuynia cordata Thunb Fraction Induces Human Leukemic Molt-4 Cell Apoptosis through the Endoplasmic Reticulum Stress Pathway

  • Prommaban, Adchara;Kodchakorn, Kanchanok;Kongtawelert, Prachya;Banjerdpongchai, Ratana
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1977-1981
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    • 2012
  • Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer. The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death. Six HCT fractions were cytotoxic to human lymphoblastic leukemic Molt-4 cells in a dose-dependent manner by MTT assay, fraction 4 exerting the greatest effects. Treatment with $IC_{50}$ of HCT fraction 4 significantly induced Molt-4 apoptosis detected by annexinV-FITC/propidium iodide for externalization of phosphatidylserine to the outer layer of cell membrane. The mitochondrial transmembrane potential was reduced in HCT fraction 4-treated Molt-4 cells. Moreover, decreased expression of Bcl-xl and increased levels of Smac/Diablo, Bax and GRP78 proteins were noted on immunoblotting. In conclusion, HCT fraction 4 induces Molt-4 apoptosis cell through an endoplasmic reticulum stress pathway.

Transfusional Iron Overload and Choroid Plexus Hemosiderosis in a Pediatric Patient: Brain Magnetic Resonance Imaging Findings

  • Kim, Min Seon;Lee, Ha Young;Lim, Myung Kwan;Kang, Young Hye;Kim, Jun Ho;Lee, Kyung Hee
    • Investigative Magnetic Resonance Imaging
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    • v.23 no.4
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    • pp.390-394
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    • 2019
  • Hemosiderosis is characterized by the deposition of excess iron in body tissues. The choroid plexus is an important part of the central nervous system that can be the primary site of iron overload. T2*-weighted gradient echo (GRE) sequence provides high sensitivity for demonstrating cerebral microhemorrhagic foci and iron deposition. In the present study, we describe the case of a 15-year-old boy with acute lymphoblastic leukemia, in whom repeated transfusion led to iron accumulation in the brain. GRE sequence effectively demonstrated hemosiderin deposition in the choroid plexus.

The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies

  • Yokota, Asumi;Huo, Li;Lan, Fengli;Wu, Jianqiang;Huang, Gang
    • Molecules and Cells
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    • v.43 no.2
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    • pp.145-152
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    • 2020
  • RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.

Synthesis of Dihydropyrrole[3,4-f]quinazoline Antifolates and Their Antitumor Activity In Vitro (Dihydropyrrolo[3,4-f]quinazoline 엽산길항제의 합성 및 In Vitro 항암활성)

  • Baek, Du-Jong
    • YAKHAK HOEJI
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    • v.50 no.4
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    • pp.278-286
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    • 2006
  • Classical dihydropyrrole[3,4-f]quinazoline antifolates 7,8 and 9, in which the tricyclic ring is structurally similar to the pteridine ring of $CH_2-THF(1)$, the cofactor of thymidylate synthase (TS), were synthesized, and their in vitro antitumor activity was evaluated by measuring the cell growth inhibitory activity against cancer cell lines. The target compounds were cytotoxic against CCRF-CEM, human T-cell acute lymphoblastic leukemia, with the cell growth inhibitory activity $(IC_{50})$ of $0.8{\sim}8.3\;{\mu}M$. Among the three compounds, 3-amino analog 7 was 10- and 3.5-fold more cytotoxic compared to the 3-methyl analogs 8 and 9, and its cytotoxicity was similar to that of the reference compound with the $IC_{50}$ value of $0.83\;{\mu}M$. This result was supposed as the consequence of the fact that dihydropyrroloquinazolinone ring with amino group was able to bind well in the active site of TS. In the case of 3-methyl analogs, analog 9, which has two-carbon bridge between the dihydropyrroloquinazolinone ring and benzoyl-L-glutamic acid, was 3-times more potent in cytotoxicity than analog 8 which has one-carbon bridge, and this result indicates that the distance and conformational orientation of the benzoyl-L-glutamic acid moiety with respect to the tricyclic ring may also be a crucial determinant of cell growth inhibitory activity.

Posttraumatic Growth of Adolescents with Childhood Leukemia and their Parents

  • Hong, Sungsil;Park, Ho Ran;Choi, Sun Hee
    • Child Health Nursing Research
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    • v.25 no.1
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    • pp.9-16
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    • 2019
  • Purpose: Childhood leukemia is a serious trauma affecting both adolescents and their parents, who experience painful process. However, adolescents with leukemia and their parents also experience positive changes, which is referred to as posttraumatic growth. We examined posttraumatic growth, core beliefs, impact of event, and event-related rumination in adolescents within 5 years of a diagnosis of childhood leukemia and their parents. Methods: The participants were 68 adolescents with childhood leukemia (aged 13~18 years) and their parents, who were recruited from C university hospital in Korea from May to September 2016. The Posttraumatic Growth Inventory, Core Belief Inventory, Impact of Event Scale-Revised, and Event-related Rumination Inventory were completed by the adolescents and their parents. The mean scores and correlations between variables were investigated for both set of participants. Results: Parents showed significantly higher levels of posttraumatic growth, disruption of core beliefs, impact of event, and invasive rumination than adolescents. Disruption of core beliefs and deliberate rumination were positively correlated with posttraumatic growth in both groups. Conclusion: Nursing intervention programs that involve modifying core beliefs and inducing a positive thought can help adolescents with leukemia and their parents grow after traumatic events.

Characterization of L-asparaginase-producing Trichoderma spp. Isolated from Marine Environments

  • Woon-Jong, Yu;Dawoon, Chung;Yong Min, Kwon;Seung Sub, Bae;Eun-Seo, Cho;Hye Suck, An;Grace, Choi
    • Journal of Marine Life Science
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    • v.7 no.2
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    • pp.121-128
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    • 2022
  • L-asparaginase (ASNase) is a therapeutic enzyme used to treat acute lymphoblastic leukemia. Currently, the most widely used ASNases are originated from bacteria. However, owing to the adverse effects of bacterial ASNases, new resources for ASNase production should be explored. Fungal enzymes are considered efficient and compatible resources of natural products for diverse applications. In particular, fungal species belonging to the genus Trichoderma are well-known producers of several commercial enzymes including cellulase, chitinase, and xylanase. However, enzyme production by marine-derived Trichoderma spp. remains to be elucidated. While screening for extracellular ASNase-producing fungi from marine environments, we found four strains showing extracellular ASNase activity. Based on the morphological and phylogenetic analyses using sequences of translation elongation factor 1-alpha (tef1α), the Trichoderma isolates were identified as T. afroharzianum, T. asperellem, T. citrinoviride, and Trichoderma sp. 1. All four strains showed different ASNase activities depending on the carbon sources. T. asperellem MABIK FU00000795 showed the highest ASNase value with lactose as a carbon source. Based on our findings, we propose that marine-derived Trichoderma spp. are potential candidates for novel ASNase production.