• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5359-5364
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• 2015

Background: Multiple complex pathways are operable in the evolution of cutaneous T cell lymphomas (CTCLs). These pathways involve interaction between neoplastic T cells and cells of the immune system (especially dendritic cells and the non-malignant T cells). Granulysin is a proinflammatory antimicrobial peptide which has an immune alarmin function, activating dendritic cells, as well as an active role in tumor immunology and prognosis. FOXP3+ regulatory T cells Tregs are an important player in the immune system. Much controversy is found in the literature about the role of Tregs in CTCL. Aim: The present study aimed to investigate the expression of granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and its leukemic form ;$s\acute{e}ezary$ syndrome (SS). Materials and Methods: Immunohistochemical expression of granulysin and FOXP3 were assessed in lesional skin biopsies taken from 58 patients (4 large plaque parapsoriasis, 48 MF and 6 SS). Results: Granulysin positivity was cytoplasmic and higher in MF than in parapsoriasis en plaque and higher in the more advanced stages of MF (p<0.001). All groups showed significant differences between each other except between MF tumor stage and SS. FOXP3 positivity was nuclear and higher in early stage MF (plaque and patch stages) than in tumor stages and SS (p<0.001). However the FOXP3 count was lower in parapsoriasis en plaque than in other stages of MF. All the groups showed significant differences between each other except between parapsoriasis and SS and between patch and plaque stages of MF. Conclusions: The present study supports a role for granulysin in MF progression and proposes a novel hypothesis about the effect of FOXP3 +veTregs in the suppression of the activity of the neoplastic cells in MF.

• Korean Journal of Agricultural Science
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• v.36 no.1
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• pp.41-50
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• 2009

Fucoidan is a uniquely-structured sulfated fucose-rich polysaccharide derived from brown algae. Recently, the abalone glycosidase-digested fucoidan extract (fucoidan extract) derived from seaweed Cladosiphon novae-caledoniae Kylin (Mozuku) draws much attention because of its clinical anti-cancer effect in Japan. Here, we report the cancer cells-specific apoptosis inducing effects of the fucoidan extract. The fucoidan extract suppressed the growth of various anchorage-dependent and -independent cancer cells. The fucoidan extract contained low molecular weight components, which induced apoptosis of human leukemic HL 60 cells but not of human lymphocytes. It was shown that the fucoidan extract lead caspase 3/7 activation and loss of mitochondrial membrane potential in HL 60 cells. Another function of the fucoidan extract was also observed. It has been known that sugar chain expression on the surface of cancer cell membrane changes dependent on their malignancy. The analysis on sugar chain expression profiling using FITC-labeled lectins revealed that the expression of concanavalin A (Con A) binding sugar chain was enhanced by the treatment of human lung adenocarcinoma A549, human uterine carcinoma HeLa and human fibrosarcoma HT1080 cells with the fucoidan extract. Con A-induced apoptosis of cancer cells was stimulated in a dose-and time-dependent manner by the treatment with the fucoidan extract but not of human normal fibroblast TIG-1 cells.

• Molecules and Cells
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• v.46 no.10
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• pp.611-626
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• 2023

Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

• Korean Journal of Food Science and Technology
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• v.30 no.3
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• pp.665-671
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• 1998

Protein-bound polysaccharides (PBP) were extracted from the mycellia of Lentinus edodes SR-1, and their anti-tumor activities and immunopotentiating properties were observed. The amounts of PBP needed to extend the doubling time twofold (1 unit) were found to be 1 mg for mouse leukemic cells $P_{388}\;and\;L_{1210}$; 4.4, 3.6 and 6.6 for bowel cancer cells, HCT-48, HRT-18, HT-29 respectively; and 2.6 mg for liver cancer cell, Hep G2. When $P_{388}\;and\;L_{1210}$ were treated with 4 mg of PBP, more than 90% of the cell number were reduced in 48 hours. However, 9 mg of PBP and 72 hrs of incubation time were needed to obtain the same effect for HRT-18, HT-29, and Hep G2. The significant reduction of cell size was observed as the amount of PBP and the incubation time increased. Mice spleen weight and plaque forming cell number increased when the cancer cells were treated with PBP.

• Clinical and Experimental Pediatrics
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• v.53 no.7
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• pp.753-758
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• 2010

Purpose: It has been suggested that p16 has a role in glucocorticoid (GC)-related apoptosis in leukemic cells, but the exact mechanisms have yet to be clarified. We evaluated the relationship between the GC response and p16 expression in a lymphoma cell line. Methods: We used p16 siRNA transfection to construct p16-inactivated cells by using the B-cell lymphoblast cell line NC-37. We compared glucocorticoid receptor (GR) expression, apoptosis, and cell viability between control (p16+NC-37) and p16 siRNA-transfected (p16-NC-37) cells after a single dose of dexamethasone (DX). Results: In both groups, there was a significant increase in cytoplasmic GR expression, which tended to be higher for p16+NC-37 cells than for p16- NC37 cells at all times, and the difference at 18 h was significant (P<0.05). Similar patterns of early apoptosis were observed in both groups, and late apoptosis occurred at higher levels at 18 h when the GR had already been downregulated ($P$<0.05). Cell viability decreased in both groups but the degree of reduction was more severe in p16+NC-37 cells after 18 h ($P$<0.05). Conclusion: These results suggest a relationship between GR expression and cell cycle inhibition, in which the absence of p16 leads to reduced cell sensitivity to DX.

• Natural Product Sciences
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• v.11 no.4
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• pp.207-212
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• 2005

Tetragonia tetragonoides (Aizoaceae) has been known as an anti-cancer agent. The activation of proteinase-activated receptor-2 (PAR-2) by trypsin appears to play a role in inflammation. In the present study, we examined the inhibitory effects of Tetragonia tetragonoides water extract (TTWE) on the production of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ and tryptase in trypsin-stimulated human leukemic mast cells (HMC-1) expressing PAR-2. HMC-1 cells were stimulated with trypsin in the presence or absence of TTWE (10, 100, and $1000\;{\mu}g/ml$). The level of $TNF-{\alpha}$ secretion from HMC-1 cells was measured by enzyme-linked immunosorbent assay (ELISA). $TNF-{\alpha}$ and tryptase mRNA expression were examined by reverse transcription-PCR. Also, extracellular signal-regulated kinese (ERK) activation was assessed by Western blot analysis. Trypsin activity was measured using the substrate Bz-DL-Arg-p-nitroanilide (BAPNA). It was observed that $TNF-{\alpha}$ secretion, tryptase mRNA and $TNF-{\alpha}$ mRNA expression in trypsin-stimulated HMC-1 cells were inhibited by pretreatment of TTWE ($1000\;{\mu}g/ml$). Furthermore, the pretreatment of TTWE ($1000\;{\mu}g/ml$) resulted in the reduction of ERK phosphorylation and trypsin activity. These results suggest hat TTWE might have the inhibitory effects on the PAR-2-dependent inflammation processes and it is likely to function as PAR-2 antagonist.

• Journal of Ginseng Research
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• v.8 no.2
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• pp.153-166
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• 1984

The anticancer activities of petroleum ether extract of Panax ginseng root(crude GX) and its partially purified fraction from silicic acid column chromatography (7:3 GX) were studied with Sarcoma 180(S-180) or Walker carcinosarcoma 256 (Walker 256) in vivo and with L1210 leukemic lympocyte in vitro. Potential cytotoxic activities of the crude GX and against L1210 cells were compared with those of 5-Fluorouracil (5-FU) and saponin derivatives (Panax-diol, Panax-triol, Diol saponin, Triol saponin) in vitro. In order to observe the physiological effects of the crude GX and 7:3 GX on the animals with cancer, hemoglobin(Hb), red blood cell(R.B.C) and white blood cell after treatment with each GX in comparison with corresponding control groups, respectively. The anticancer effects of the crude GX and 7:3 GX were estimated by measuring the survival time of S-180 bearing mice after treatment with them. The experimental results obtained are summarized as follows; 1. The one unit of cytotoxic activity against L1210 cells was equivalent to 2.54$\mu\textrm{g}$ and 0.88$\mu\textrm{g}$of the crude GX and 7:3 GX per ml of culture medium, respectively. 2. The cytotoxic activities of Panax-diol, Panax=triol, Diol saponin and triol saponin against L1210 cells were not detected. 3. The anticancer activities of 5-FU against L1210, S-180 and Walker 256 were very effective in vivo and vitro tests. 4. The significantly increased W.B.C values of mice after inoculation with S-180 cells were reduced to normal range by the crude GX treatment. 5. The significantly decreased Hb values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude GX. 6. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7:3 GX treatment compared with their control group.

• Proceedings of the Korean Society of Life Science Conference
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• 2006.09a
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• pp.98.1-98.1
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• 2006

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.97.2-97.2
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• 2008

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.48.1-48.1
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• 2008