• Radiation Oncology Journal
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• v.19 no.2
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• pp.153-162
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• 2001

Purpose : The mechanical insights of death of cancer cells by ionizing radiation are not of yet clearly defined. Recent evidences have demonstrated that radiation therapy may induce cell death via activation of signaling pathway for apoptosis in target cells. This study is designed whether ionizing radiation may activate the signaling cascades of apoptosis including caspase family cysteine pretenses, $Bcl_2/Bax$, cytochrome c and Fas/Fas-L in target cells. Materials and Methods : HL-60 cells were irradiated in vitro with 6 MV X-ray at dose ranges from 2 Gy to 32 Gy. The cell viability was tested by M assay and the extent of apoptosis was determined using agarose gel electrophoresis. The activities of caspase proteases were measured by proteolytic cleavages of substrates. Western blot analysis was used to monitor PARP, Caspase-3, Cytochrome-c, Bcl-2, Bax, Fas and Fas-L. Results : Ionizing radiation decreases the viability of HL-60 cells in a time and dose dependent manner. Ionizing radiation-induced death in HL-60 cells is an apoptotic death which is revealed as characteristic ladder-pattern fragmentation of genomic DNA over 16 Gy at 4 hours. ionizing radiation induces the activation of caspase-2, 3, 6, 8 and 9 of HL-60 cells in a time-dependent manner. The activation of caspase-3 pretense is also evidenced by the digestion of poly (ADP-ribose) polymerase and procaspase 3 with 16Gy ionizing irradiation. Anti-apoptotic Bcl2 expression is decreased but apoptotic Bax expression is increased with mitochondrial cytochrome c release in a time- dependent manner. In addiiton, expression of Fas and Fas-L is also increased in a time dependent manner. Conclusion : These data suggest that ionizing radiation-induced apoptosis is mediated by the activation of various signaling pathways including caspase family cysteine proteases, $Bcl_2/Bax$, Fas and Fas-L in a time and dose dependent manner.

• Journal of Life Science
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• v.16 no.3 s.76
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• pp.546-554
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• 2006

To understand antitumor activity of Zanthoxylum schinfolium, which has been used as an aromatic and medicinal plant in Korea, the cytotoxic effect of various organic solvent extracts of its leaves on human tumor cells were investigated. Among these extracts such as methanol extract (SL-13), methylene chloride extract (SL-14), ethyl acetate extract (SL-15), n-butanol extract (SL-16), and residual fraction (SL-17), SL-14 appeared to contain the most cytotoxic activity against leukemia and breast cancer cells tested. The methylene chloride extra.1 (SL-14) possessed an apoptogenic activity causing apoptotic DNA fragmentation of human acute leukemia Jurkat T cells via mitochondrial cytochrome c release into cytoplasm, subsequent activation of caspase-9 and caspase-3, and cleavage of PARP, which could be negatively regulated by antiapoptotic protein Bcl-xL. The GC-MS analysis of SL-14 revealed that the twenty-two ingredients of SL-14 were 9,19-cyclolanost-24-en-3-ol (15.1%), 2-a-methyl-17, b-hop-21-ene (15.1%), 15-methyl-2,3-dihydro-1H benzazepin (11.95%), phytol (10.38%), lupeol (9.92%), 12-methylbenzofuran (8.23%), hexadecanoic acid (5.96%), cis,cis,cis-9,12,15-octadecatrienoic acid-methyl-ester (5.49%), 9,12,15-octadecatrienoic acid-methylester (3.59%), 15-methyl-4-(1-methylethylidene)-2-(4-nitrophenyl) (3.36%), hexadecanoic acid methyl ester (1.93%), vitamine E (1.88%), beta-amyrin (0.96%), and auraptene (0.89%). These results demonstrate that the cytotoxicity of the methylene chloride extract of the leaves of Z. schinifolium toward Jurkat T cells is mainly attributable to apoptosis mediated by mitochondria-dependent caspase cascade regulated by Bcl-xL, and provide an insight into the mechanism underlying antitumor activity of the edible plant Z. schinifolium.

• KSBB Journal
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• v.22 no.1
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• pp.22-29
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• 2007

The water-soluble materials extracted from fruit bodies and mycelium of H. erinaceum were prepared. In-vitro anticancer activities on cancer cells and In-vivo proliferation effect on mouse peritoneal exudate cell and spleen cell of samples were investigated. Also, nitric oxide (NO) generation of peritoneal exudate cell, IL-2 production capacity of spleen cells and phagocytic activity of peritoneal macrophages were examined. The water extracts of H. erinaceum suppressed the proliferation of cancer cell (HeLa, Raw264.7, Jurkat, KATO3, EL4, LyD9) with concentration-dependent. The water extract from fruit body showed better suppression effect than that from mycelium in most of cancer cells used. The anticancer effect of water extract of fruits body in the range of 0.01 and 10 mg/ml for Raw 264.7 and EL4 cell lines were the same as the Taxol with one thousandth equivalent of fruit body concentration. Water extracts of fruit body and liquid-cultured products of H. erinaceum induced nitric oxide (NO) generation of peritoneal exudate cell and increased NO generation by stimulus of lipopolysaccharide. Water extracts alone did not induce the proliferation and IL-2 production capacity of spleen cells. However, spleen's proliferation and IL-2 production were induced significantly by the addition of lipopolysaccharide and Con A (concanavalin A) or Con A alone, and the effectiveness of mycelium extract with water were more active than those from fruit body.

• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.428-436
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• 2003

Purpose: Increased periarticular uptake could be associated with peripheral bone marrow expansion in cancer patients with axial bone marrow metastasis. We compared bone scan and bone marrow scan to investigate whether the increased whole body count in patients with increased periarticular uptake on bone scan is useful in the diagnosis of axial marrow metastasis, and evaluate the role of additional bone marrow scan in these cases. Materials and methods: Twelve patients with malignant diseases who showed increased periarticular uptake on bone scan were included. Whole body count was measured on bone scan and it is considered to be increased when the count is more than twice of other patients. Bone marrow scan was taken within 3-7 days. Results: Five hematologic malignancy, 3 stomach cancer, 2 breast cancer, 1 prostate cancer and 1 lung cacner were included. All three patients with increased whole body count on bone scan showed axial marrow suppression and peripheral marrow expansion. Eight of 9 patients without increased whole body count showed axial marrow suppression and peripheral marrow expansion. One turned out to be blastic crisis of chronic myelogeneous leukemia, and seven showed normal axial marrow with peripheral marrow expansion in chronic anemia of malignancy. The last one without increased whole body count showed normal bone marrow scan finding. Conclusion: Increased whole body count on bone scan could be a clue to axial bone marrow metastasis in cancer patients with increased periarticular uptake, and bone marrow scan is a valuable method for differential diagnosis in these cases.

• Clinical and Experimental Pediatrics
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• v.45 no.8
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• pp.1007-1015
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• 2002

Purpose : The aim of this study is to find a method to diagnose and treat children who showed benign hemophagocytic histiocytes in bone marrow examination. Methods : We analyzed the clinical data of thirty patients retrospectively who showed benign hemophagocytic histiocytes in bone marrow examination from January 1995 to November 2001 at Keimyung University Dong-san Hospital. Bone marrow histiocytes were classified into a few, some, and many according to the number of histiocytes comparing with the white cells. Results : The age of thirty patients ranged from two months to 15 years. The median age was 5.6 years with male predominance(2.3 : 1). The most frequent clinical manifestation was fever; others were respiratory symptom, hepatosplenomegaly, lymphadenopathy and skin rash(in order of frequency). Common laboratory findings were leukopenia, thrombocytopenia, anemia and abnormal liver function test. Infection was present in 30 patients; causative organisms were documented in 15 patients, and bacterial infection was more common. Epstein Barr virus was the cause of infection in four patients. Bone marrow examination showed a few(20.0%), some(75.0%) and many(30.0%) hemophagocytic histiocytes. Combination immunochemotherapy including immunoglobulin, steroids and cyclosporine were helpful in 22 out of 30 patients. The mortality rate was high in young patients who showed some to many hemophagocytic histiocytes. Conclusion : Bone marrow examinations and early detection of histiocytes will be helpful in children who have fever, hepatosplenomegaly and abnormal liver function test. Immunochemotherapy were helpful and further investigation will be needed for the detection of the relationship between the bone marrow findings and prognosis.

• Pediatric Infection and Vaccine
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• v.15 no.1
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• pp.36-44
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• 2008

Purpose : Orbital cellulitis is rare, but it could be from the serious complication of sinusitis in children. It is often difficult to distinguish periorbital cellulitis from orbital cellulitis. The purpose of this study is to describe the clinical features of orbital and periorbital cellulitis in a pediatric population and to assess the predisposing factors and their complications. Methods : Forty-one patients aged 18 years and younger who were admitted between January 2000 and December 2006 to Hanil General Hospital and Kyunghee University Hospital with orbital or periorbital cellulitis. The retrospective analyses included clinical characteristics of orbital and periorbital cellulitis, dermographics, past history, predisposing factors, clinical presentations, treatments, and complications. Results : Among 41 patients, 34 patients had periorbital cellulitis, 7 patients had orbital cellulitis. While paranasal sinus disease was the most common predisposing cause in orbital cases, skin lesion, insect bite, dacrocystitis and conjunctivitis were the common causes in periorbital cases. In comparison with periorbital cases, orbital cases had higher level of white blood cell count, erythrocyte sedimentation rate, and C-reactive protein. Blood cultures were taken in 23 patients, but only one had Staphylococcus aureus from blood. Only one case had surgical incision and drainage and recovered without complications. Conclusion : From the results of our data, when patient shows erythematous swelling of periorbital area with opthalmoplegia, chemosis and proptosis, orbital CT scan is required to make diagnosis of orbital cellulitis. Most cases of orbital cellulitis can be treated successfully without surgical intervention. If there is no clinical improvement, repeated CT scan and/or surgical intervention should be considered.

• Journal of Music and Human Behavior
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• v.2 no.2
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• pp.15-31
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• 2005

Terminal pediatric patient include congenital metabolic abnormalities, chromosome aberrations, congenital anomalies, neuromuscular diseases and other incurable conditions as well as malignant tumors. One third of these diseases are cancers, and two thirds of cancers are lymphadenoma and leukemia. Terminal pediatric patient may feel fear, anger and frustration against treatment process in hospitals, lose control of themselves and stay in helplessness due to restrictions within controlled hospital environment. This study examined the relationship between hospitalized childrens behavior and music using Contextual Support Model of Music Therapya theory stating therapeutic music environments possess three elements of Structure, Autonomy support and Involvement, and increase childrens active engagement. Focused on these three therapeutic elements, this study analyzed music therapy cases of terminally ill children to examine the relationship between childrens behavior and music as environmental supportive medium in the environment. This study is on a single case case subject, a 10-year-old girl with acute lymphocytic leukemia. Nine sessions of music therapy activities were conducted and analyzed using qualitative method. Focusing on three therapeutic elements of Contextual Support Model, analysis of sessions was made on the basis of activities specifically designed for this study. Main music therapy activities included singing while playing musical instruments, singing while listening to music through CD player, making up songs, and searching for song lines. The findings of this study are as follows: a) in terms of Structure, music therapy suggested a direction for effective musical activities for terminally ill children by providing environments where child can sing, play musical instruments and make up songs; b) in terms of Autonomy support, music therapy encouraged childs voluntary participation by giving her chances to make choice while singing or playing musical instruments; c) in terms of Involvement, child could gain positive approval of the therapist and conduct musical activities in cooperation with the therapist. Music therapy serves as supportive medium in the environment, develops spontaneity and self-reliance in emotionally depressed children, and promotes voluntary attitudes in the restricted hospital environment. Based on the positive effects of music therapy, more studies need to be conducted with an approach to more various terminal pediatric patients.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.181-186
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• 2006

Purpose : The hematologic change during the treatment of acute lymphoblastic leukemia(ALL) is critical as a prognostic determinant and a variable to determine the dose of chemotherapeutic agents. It is known that the dose of vincristine used in the maintenance phase of ALL is small enough to increase the count of platelet. To investigate the change of platelet count according to the vincristine administration in maintenance phase of ALL chemotherapy, we performed this study. Methods : Eleven patients eligible under the criteria of Children's Cancer Study Group(CCG)-1882 and who had completed chemotherapy were enrolled in this study. The count of platelets before vincristine administration was compared with those of vincristine administration 1, 2 and 3 weeks after the early and last periods of maintenance phases. The platelet count before vincristine administration was defined as 100 percent and that after vincristine were compared. In addition, we tentatively defined an enhancing effect of vincristine as positive when the relative count was more than 120 percent. Results : Platelet count did not differ according to the early and last periods of maintenance phase. Platelet count at first week after vincristine administration increased more significantly than that before vincristine in early and last periods. There was an enhancing effect in 10(90.9 percent) of 11 patients after 1 week vincristine administration both in the early and last periods of the maintenance phase. Conclusion : Vincristine, used in ALL maintenance phases as a low dose, increased platelet count 1 week after administration. The increased platelet count resumed to the previous level 2-3 weeks later. However, the thrombocytosis observed in the maintenance phase by vincristine was not high enough to induce thrombosis. In addition, vincristine is known to reduce the activity of platelets. Therefore, the risk of thrombosis in the maintenance phase of ALL chemotherapy would be low.

• Journal of Life Science
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• v.21 no.12
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• pp.1678-1688
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• 2011

The apoptogenic effect of p-coumaric acid, a phenolic acid found in various edible plants, on human acute leukemia Jurkat T cells was investigated. Exposure of Jurkat T cells to p-coumaric acid (50-$150{\mu}M$) caused cytotoxicity and TdT-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic DNA fragmentation along with Bak activation, ${\Delta}{\psi}m$ loss, activation of caspase-9, -3, -7, and -8, and PARP degradation in a dose-dependent manner. However,these apoptotic events were completely abrogated in Jurkat T cells overexpressing Bcl-2.Under these conditions, necrosis was not accompanied. Pretreatment of the cells with the pan-caspase inhibitor (z-VAD-fmk) could prevent p-coumaric acid-induced sub-$G_1$ peak representing apoptotic cells, whereas it failed to block ${\Delta}{\psi}m$ loss, indicating that the activation of caspase cascade was prerequisite for p-coumaric acid-induced apoptosis as a downstream event of ${\Delta}{\psi}m$ loss. FADD- and caspase-8-positive wild-type Jurkat T cell clone A3, FADD-deficient Jurkat T cell clone I2.1, and caspase-8-deficient Jurkat T cell clone I9.2 exhibited similar susceptibilities to the cytotoxicity of p-coumaric acid, excluding an involvement of Fas/FasL system in triggering the apoptosis. The apoptogenic activity of p-coumaric acid is more potent in malignant Jurkat T cells than in normal human peripheral T cells. Together, these results demonstrated that p-coumaric acid-induced apoptogenic activity in Jurkat T cellswas mediated by Bak activation, ${\Delta}{\psi}m$ loss, and subsequent activation of multiple caspases such as caspase-9, -3, -7, and-8, and PARP degradation, which could be regulated by anti-apoptotic protein Bcl-2.