• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.31-36
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• 2012

The receptor activator of NF-${\kappa}B$ ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-${\kappa}B$ and other signal transduction pathways essential for osteoclastogenesis, such as $Ca^{2+}$ signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate ($IP_3$) and $IP_3$-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of $IP_3$ and evaluated $IP_3$-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of $Ca^{2+}$ signaling proteins such as $IP_3$ receptors ($IP_3Rs$), plasma membrane $Ca^{2+}$ ATPase, and sarco/endoplasmic reticulum $Ca^{2+}$ ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of $IP_3$ was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) ${\delta}$, a probe specifically detecting intracellular $IP_3$ levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)[ and of $IP_3Rs$ with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of $IP_3Rs$) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular $IP_3$ levels and the $IP_3$-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.407-412
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• 2010

3-Deazaadenosine (DZA), a potent inhibitor of S-adenosylhomocysteine hydrolase, was previously proposed to induce intrinsic apoptosis in human leukemic cells. In the present study, we analyzed the mechanism underlying the DZA-induced intrinsic apoptotic pathway. DZA activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an accumulation of hypo-diploidic cells, the processing of multiple procaspases and an inhibitory effect of z-VAD-Fmk on this cell death. During DZA-induced apoptosis, cytochrome c (cyt c) was released into the cytosol. This was neither prevented by z-VAD-Fmk and nor was it associated with the dissipation of mitochondrial membrane potential (${\Delta}{\Psi}_m$). Prior to the release of cyt c, BAX was translocated from the cytosol to mitochondria and underwent oligomerization. Finally, the overexpression of BCL-XL protected HL-60 cells from apoptosis by blocking both the cyt c release and BAX oligomerization. Collectively, these findings suggest that DZA may activate intrinsic apoptosis by stimulating BAX activation and thereby the release of cyt c.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.310-312
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• 2000

Leukemia is a malignancy caused by precursor cells of white blood cell. It is a malignant tumor of hematopoietic organs, characterized by the disorder of hematopoietic function due to the proliferation of immature bone marrow cells or lymphatic cells and by abnormal tissue infiltration of leukemic cells. The major signs of leukemia are caused by the failure of bone marrow function. As the number of red blood cells decreases, anemia is to appear. The number of white blood cells in leukemia is usually increased but immature white blood cells circulating the body has little defense ability, thus become susceptible to infection. 27 year-old female patient who was treated chemotherapy and bone marrow transplantation after diagnosed as chronic myelogenous leukemia(CML) was diagnosed as osteomyelitis in mandible after clinical and dental radiographic film examination. Because of the result of examination, the involved tooth of the patient was extracted accompanied by sequestrectomy and saucerization under general anesthesia. After the patient had long term medication of antibiotics, the lesion was healed. Therefore. author, et al. report this case with literature review.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.6
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• pp.535-540
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• 2009

Proliferation of abnormal hematopoietic cells with impaired differentiation, regulation and programmed cell death leads to leukemia. AML(acute myeloid leukemia) is a malignancy with malfunction of myeloid hematopoietic cells with acute behavior. The oral manifestations of the disease are posterior palate hemorrhage, gingival bleeding and gingival ulceration as a result of infection by normal oral flora and gingival infiltration by leukemic cells. A 49-year-old male patient was referred from local dental clinic. The patient was diagnosed with AML FAB M1 (acute myeloid leukemia French-American-British classification M1 myeloblastic leukemia without maturation). The oral infection focus was removed by a conservative treatment. 2 days after the dental treatment, the patient underwent chemotherapy. At 8-month follow-up, the overall outcome was excellent. Oral manifestations of AML are often the first indications of the malignancy. Therefore it is essential for dentists, especially oral and maxillofacial surgeons, to be aware of the diagnostic signs and complications associated with leukemia for better diagnosis and subsequent treatment and management.

• The Journal of Pediatrics of Korean Medicine
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• v.18 no.2
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• pp.31-48
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• 2004

Objective : KagamJwagwiEum(KJE) has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in Korea. To investigate the biological effect of KJE, the author examined cytotoxicity and inflammatory cytokines secretion with human leukemic mast cell line, HMC-1. Methods: HMC-1 was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. KJE by itself had no effect on viability of HMC-l. The effects of KJE on the secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$, interleukin(IL)-6 and IL-8 from HMC-1 were evaluated with enzyme-linked immunosorbent assay. Results : KJE inhibited PMA plus A23187-induced $TNF-{\alpha}$ and IL-6 secretion. But KJE had no effect IL-8 secretion: KJE had immunoregulatory effects on cytokines, increased secretion of NO and $TNF-{\alpha}$ but did not effect IL-12 secretion when the cells were primed and trigged with $IFN-{\gamma}$ in the peritoneal macrophages of C57BL/6 mice. Conclusions : Taken together, these results suggest that KJE inhibit the production of inflammatory cytokines in HMC-1 cells and activate macrophages.

• Advances in Traditional Medicine
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• v.7 no.4
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• pp.341-347
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• 2007

Red seaweed (Callophyllis japonica) has long formed part of the diet of Asians, but the pharmacological properties of this plant have not been evaluated. In this study, we examined the effect of an ethanol extract of C. japonica on the generation of nitric oxide (NO) in RAW 264.7 cells. The C. japonica extract increased the generation of NO and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), which were detected by the Griess method and an enzyme-linked immunosorbent assay, respectively. The increased production of NO by C. japonica extract was inhibited by $N^G$-monomethyl-L-arginine ($100{\mu}M$), a specific inhibitor of NO production in the L-arginine-dependent pathway, and by the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) inhibitor, pyrrolidine dithiocarbamate ($10-100{\mu}M$) in a dose-dependent manner. These findings demonstrate that C. japonica extract stimulates the production of NO and $TNF-{\alpha}$ in RAW 264.7 cells through the activation of $NF-{\kappa}B$ and that this extract might also inhibit the growth of the human leukemic cells.

• 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.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.49-52
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• 2002

Background: The possibility that G-CSF recruits leukemic cells from the G0 to S phase, which may lead to a greater susceptibility to cytotoxic drugs, such as ara-C, has been presented in Harada's study. Methods: In this study, we referred to the protocol of Harada et al 1 to try G-CSF combined marrow-ablative chemotherapy and autologous PBSCT, for the treatment of AML patients in CR1 status. Between January 1997 and March 1998, six AML patients (3: children, 3: adults) in CR1 status were autografted and followed up to 3 years. Results: The major regimen related toxicity was composed of mucositis and diarrhea without death. The time of ANC recovery to 500/L and 1,000/L was 11~48 and 16~81 days, respectively. The mean time of platelet recovery to 20,000/L and 50,000/L was 21~233 and 35~370 days, respectively. The platelet recovery time to 50,000/L was markedly prolonged for more than 100 days in four patients (66.7%). Moreover, four patients (66.7%) experienced a relapse of leukemia after transplantation, with a mean interval of 147.5 days after PBSCT. Two patients were in CR status for 53 and 51 months after PBSCT, respectively. Conclusion: The G-CSF combined marrow-ablative chemotherapy and autologous PBSCT resulted in a markedly delayed platelet recovery and no advantages for decreasing the relapse rate of AML. But, further studies will be warranted.

• YAKHAK HOEJI
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• v.50 no.6
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• pp.372-380
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• 2006

Farnesol in fruits, vegetables, herbs and leaves acts as bioactive component related with prevention of cancer and psychological malaise. We investigated the cytotoxic effects of farnesol on human leukemic cell, HL-60 cells, by MTT assay using 3- (4,5-Oirnethylthiazol-2-yl) -2,5-diphenyltetrazoliumbromide. Farnesol (0.1${\sim}$50 ${\mu}$g/ml) exhibited cytotoxicities against HL-60 cells in concentration and culture period dependent manner, In the cytotoxic condition induced by farnesol against HL-60 cells, the generation of reactive oxygen species such as O$_2$ and H$_2$O$_2$ were found to be considerably increased. The most prominent augmentations of O$_2$ and H$_2$O$_2$ were over five folds of controls. In an attempt to explore the response of HL-60 cells to the increased O$_2$ and H$_2$O$_2$, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities of HL-60 cells treated with farnesol were measured. SOD and GPx activities were found to be remarkably elevated by addition of farnesol showing the best results of 273% and 167% of controls, respectively: All data suggest that farnesol may have played as an apoptosis inducer in HL-60 cells via production of reactive oxygen species (ROS) and HL-60 cells may have failed to overcome the damage of ROS on account of still defcient ROS scavengers including SOD and GPx.

• Journal of Life Science
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• v.23 no.9
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• pp.1118-1125
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• 2013

Naringenin, a naturally occurring citrus flavonone, is a potentially valuable candidate for cancer chemotherapy. However, the cellular and molecular mechanisms responsible for its anticancer activity are largely unknown. In the present study, we attempted to elucidate the mechanisms responsible for naringenin-induced apoptosis in human leukemic U937 cells. We found that naringenin markedly inhibited the growth of U937 cells by decreasing cell proliferation and inducing apoptosis, which was associated with the activation of caspases. A pan-caspase inhibitor, z-VAD-fmk, significantly inhibited naringenin-induced U937 cell apoptosis, indicating that caspases are key regulators of apoptosis in response to naringenin in U937 cells. Although the levels of antiapoptotic Bcl-2 and proapoptotic Bax proteins remained unchanged in naringenin-treated U937 cells, Bcl-2 overexpression attenuated naringenin-induced apoptosis. Furthermore, combined treatment with naringenin and HA14-1, a small-molecule Bcl-2 inhibitor, effectively increased the apoptosis through enhancement of XIAP down-regulation, Bid cleavage, and caspase activation, suggesting that the synergistic effect was at least partially mediated through the death receptor-mediated apoptosis pathway.