• Title/Summary/Keyword: DCs

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Dendritic Cell Based Cancer Immunotherapy: in vivo Study with Mouse Renal Cell Carcinoma Model (수지상세포를 이용한 항암 면역 치료: 생쥐 신장암 모델을 이용한 연구)

  • Lee, Hyunah;Choi, Kwang-Min;Baek, Soyoung;Lee, Hong-Ghi;Jung, Chul-Won
    • IMMUNE NETWORK
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    • v.4 no.1
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    • pp.44-52
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    • 2004
  • Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

Enhanced Induction of T Cell Immunity Using Dendritic Cells Pulsed with HIV Tat and HCMV-pp65 Fusion Protein In Vitro

  • Park, Jung-Sun;Park, Soo-Young;Cho, Hyun-Il;Sohn, Hyun-Jung;Kim, Tai-Gyu
    • IMMUNE NETWORK
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    • v.11 no.3
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    • pp.182-189
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    • 2011
  • Background: Cytotoxic T lymphocytes (CTLs) appear to play an important role in the control and prevention of human cytomegalovirus (HCMV) infection. The pp65 antigen is a structural protein, which has been defined as a potential target for effective immunity against HCMV infection. Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (Tat) into protein facilitates rapid, efficient entry into cells. Methods: To establish a strategy for the generation of HCMV-specific CTLs in vitro, recombinant truncated N- and C-terminal pp65 protein (pp65 N&C) and N- and C-terminal pp65 protein fused with Tat (Tat/pp65 N&C) was produced in E.coli system. Peripheral blood mononuclear cells were stimulated with dendritic cells (DCs) pulsed with pp65 N&C or Tat/pp65 N&C protein and immune responses induced was examined using IFN-${\gamma}$ ELISPOT assay, cytotoxicity assay and tetramer staining. Results: DCs pulsed with Tat/pp65N&C protein could induce higher T-cell responses in vitro compared with pp65N&C. Moreover, the DCs pulsed with Tat/pp65 N&C could stimulate both of $CD8^+$ and $CD4^+$ T-cell responses. The T cells induced by DCs pulsed with Tat/pp65 N&C showed higher cytotoxicity than that of pp65-pulsed DCs against autologous lymphoblastoid B-cell line (LCL) expressing the HCMV-pp65 antigen. Conclusion: Our results suggest that DCs pulsed with Tat/pp65 N&C protein effectively induced pp65-specific CTL in vitro. Tat fusion recombinant protein may be useful for the development of adoptive T-cell immunotherapy and DC-based vaccines.

The Effect of the Pedicle-Facet Angle on Degenerative Cervical Spondylolisthesis

  • Kim, Hyung Cheol;Jun, Hyo Sub;Kim, Ji Hee;Chang, In Bok;Song, Joon Ho;Oh, Jae Keun
    • Journal of Korean Neurosurgical Society
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    • v.58 no.4
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    • pp.341-345
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    • 2015
  • Objective : To measure the orientation of the facet joints of cervical spine (C-spine) segments in the sagittal plane, known as the pedicle-facet (P-F) angle, and to use these measurements to evaluate the relationship between the P-F angle and the amount of vertebral anterolisthesis in patients with degenerative cervical spondylolisthesis (DCS). Methods : A retrospective case-control study was performed including 30 age- and sex-matched patients with DCS and 30 control participants. Anterior-posterior and lateral view radiographs of the C-spine were obtained in a standing position. The P-F angle at all cervical levels and the amount of anterolisthesis at C4-5 were measured from lateral view plain radiographs. Results : The P-F angles at C4-5 were $141.14{\pm}7.14^{\circ}$ for the DCS group and $130.53{\pm}13.50^{\circ}$ (p=0.012) for the control group, and at C5-6 were $137.46{\pm}8.53^{\circ}$ for the DCS group and $128.53{\pm}16.01^{\circ}$ for the control group (p=0.001). The mean P-F angle at C4-5 did not correlate with the amount of anterolisthesis (p=0.483). The amount of anterior slippage did correlate with age (p<0.001). Conclusion : The P-F angle was intrinsically higher at C4-5, compared to C5-6, in both the DCS and control groups, which might explain the increased likelihood for anterolisthesis of C4. Higher P-F angles in the DCS group may be a predisposing factor to slippage. The P-F angle may interact with age to increase incidence of anterolisthesis with increasing age.

A Double-Blind, Sham-Controlled, Pilot Study to Assess the Effects of the Concomitant Use of Transcranial Direct Current Stimulation with the Computer Assisted Cognitive Rehabilitation to the Prefrontal Cortex on Cognitive Functions in Patients with Stroke

  • Park, See-Hyun;Koh, Eun-Jeong;Choi, Ha-Young;Ko, Myoung-Hwan
    • Journal of Korean Neurosurgical Society
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    • v.54 no.6
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    • pp.484-488
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    • 2013
  • Objective : To examine the synergistic effects of both computer-assisted cognitive rehabilitation (CACR) and transcranial direct current stimulation (tDCS) on cognitive function in patients with stroke. Methods : The current double-blind, sham-controlled study enrolled a total of 11 patients who were newly diagnosed with stroke. The patients of the tDCS group (n=6) completed sessions of the Korean computer-assisted cognitive rehabilitation program five times a week for 30 minutes a session during a mean period of 18.5 days concomitantly with the anodal tDCS over the bilateral prefrontal cortex combined with the CACR. The patients of the control group (n=5) also completed sessions of the sham stimulation during a mean period of 17.8 days. Anodal tDCS over bilateral prefrontal cortex (F3 and F4 in 10-20 EEG system) was delivered for 30 minutes at an intensity of 2 mA. Cathode electrodes were applied to the non-dominant arm. All the patients were evaluated using the Seoul Computerized Neuropsychological Test (SCNT) and the Korean Mini-Mental State Examination. Results : Mann-Whitney U test revealed a significant difference between the two groups. The patients of the tDCS group achieved a significant improvement in the post/pre ratio of auditory continuous performance test and visual continuous performance test on the SCNT items. Conclusion : Our results indicate that the concomitant use of the tDCS with CACR to the prefrontal cortex may provide additional beneficial effects in improving the cognitive dysfunction for patients with stroke.

Immunomodulatory activity of acharan sulfate isolated from Achatina fulica

  • Kim, Hyeon-Seon;Lee, Jae-Kwon;Yang, In-Ho;Lee, Young-Ran;Shin, Hyun-Jeong;Park, Eun-Ju;Park, Hyung-Seok;Kim, Yeong-Shik;Lee, Chong-Kil
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.307.2-308
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    • 2002
  • Acharan sulfate. a new glycosaminoglycan(GAG) isolated from the giant African snail Achatina fulica. was shown to have antitumor activity in vivo. To elucidate the mechanisms for the antitumor activity. we examined its impact on professional antigen presenting cells such as macrophages and dendritic cells (DCs). Acharan sulfate stimulated cytokine production (TNF-a and IL -1b). nitric oxide release. and morphological changes in a dose dependent manner on a macrophage cell Line Raw 264.7 cells. The differentiation-inducing activity of acharan sulfate was examined on immature DCs. Immature DCs were generated from mouse bone marrow (BM) cells by culturing with GM-CSF and IL-4, and then stimulated with acharan sulfate. The resultant DCs were then examined for funcional and phenotypic properties. It was found that acharan sulfate could induce functional maturation of immature DCs as determined by increased allogenic mixed lymphocyte reaction (MLR) and IL-12 production. Phenotypic. analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2 and CD40 also confirmed that acharan sulfate could induce maturation of immature DCs. These results suggest that that the antitumor activity of acharan sulfate is at least in part due to activation adn induction of differentiation of professinal antigen presenting cells. (omitted)

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The Effects of tDCS and Montoya Stair Task on Sensorimotor Recovery and GFAP Expression in MCAo induced Stroke Rat Model

  • Sim, Ki-Cheol;Kim, Gi-Do;Kim, Kyung-Yoon;An, Ho-Jung;Lee, Joon-Hee;Min, Kyoung-Ok;Kim, Gye-Yeop
    • Journal of International Academy of Physical Therapy Research
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    • v.2 no.1
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    • pp.193-200
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    • 2011
  • This study is intended to examine the tDCS and Montoya stair task(MST) on sensorimotor recovery and glial scar expression in MCAo induced stroke model of rat. To achieve this goal, this study selected 80 SD rats of 8 weeks. The experiment groups were divided them into four groups, and assigned 20 rats to each group. Group I was a experimental control group; GroupII was a tDCS application group after MCAo; Group III was a MST application group after MCAo; Group IV was a tDCS and MST application group after MCAo. In each group, neurological function test measurement, motor behavior test, montoya stair task test, immunohistochemistric finding of GFAP expression finding were analyzed. In motor behavior test, the outcome of group I was significantly difference than the other group, especially from 14days. In montoya stair task test, the outcome of group I was significantly lower than the other group especially, group II were significantly different on 14days and group IV was most significantly difference than the other group. In immunohistochemistric finding, group II, III, IV were decrease GFAP expression on depend on time stream. These results throughout the MCAo due to focal ischemic brain injury rat model four weeks tDCS and MST was applied, when the neurobehavioural, upper extremity function and ability, histopathologic data suggest that sensorimotor function recovery and a positive influence on glial scar decrease and confirmed that.

Effect of Sopung-tang and tDCS on Motor function Recovery and GDNF Expression in Photothrombotic Brain Infarction Induced Rat Model (광혈전 유도 뇌손상 백서에서 소풍탕(疏風湯)과 tDCS의 적용이 운동기능회복과 GDNF 발현에 미치는 영향)

  • Sim, Ki Cheol;Kim, Gi Do;Kim, Kyung Yoon;Chung, Hun Woo;Kim, Gye Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.6
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    • pp.894-901
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    • 2012
  • The effect of Sopung-tang(SPT) and trans-cranial direct current stimulation(tDCS) was investigated in photothrombotic brain infarction(PTI) rats. Sprague-Dawley 80 rats, were divided into four groups. group I was experiental control group(n=20), group II was PTI induced and oral administration of SPT(n=20), group III was PTI induced and tDCS administration(n=20) and group IV was PTI induced and SPT and tDCS administration for 28 days on stroke rats(n=20). Analysis the neurological function test, 25 point behavior functional score test, and immunohistochemistric finding of GDNF expression, and electron microscopy assessment In motor behavior test, the outcome of group IV was significantly difference than the other group, and In immunohistochemistric finding, group II, III, IV were increase GDNF expression on 28 days, In electron microscopy finding, the all groups were degenerated of cell organelles, and synaptic plasticity were improvement of group II, III, IV(especially group IV) These results suggest that, 28days application of SPT and tDCS was the motor function and histopathologic, micro-morphological improvement of motor function recovery and positive influence on synaptic plasticity.

Analgesic Effects of Transcranial Direct Current Stimulation on Central Neuropathic Pain in Spinal Cord Contusive Rat Model

  • Kim, Kyung-Yoon;Sim, Ki-Chol;Kim, Hyun-Seung;Choi, Wan-Suk;Kim, Gi-Do
    • International Journal of Contents
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    • v.8 no.1
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    • pp.74-81
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    • 2012
  • The aim is to investigate the analgesic effect of transcranial direct current stimulation(tDCS) on central neuropathic pain(CNP) in spinal cord contusive rat model. Twenty Sprague-Dawley rats($250{\pm}50$ g, male) were used. Thoracic spinal cord(T10) was contused using New York University(NYU) spinal cord impactor. The animals were randomly assigned to two groups; GroupI: Non-treatment after SCI induction(n=10), GroupII: application of tDCS(0.1 mA, 20 min/time, 2 times/day, 5 days/6week) after SCI induction(n=10). Assess the effect of tDCS using the Basso Beattie Bresnahan(BBB) locomotor rating scales, Touch $test^{TM}$ sensory evaluator(TTSE), Plantar test$^{\circledR}$after contusion at the $2^{nd}$, $3^{rd}$, $4^{th}$, $5^{th}$, $6^{th}$ week and the immunohistochemistric response of c-fos in the thalamus, cerebral cortex after contusion at the $3^{rd}$, $6^{th}$ week after SCI. The scores of BBB scales were significantly different from $3^{rd}$week. TTSE were different significantly over time, but there were no differences at each evaluation times on between-measure time effects. Plantar test were different significantly over time and there were difference at the $4^{th}$, $6^{th}$ week after SCI on between-measure time effects. Also, immunohistochemistric response of c-fos was reduced significantly from $3^{rd}$, $6^{th}$ week after SCI in tDCS group compared with control group in thalamus and cortex. These results identified that tDCS of non-invasive therapeutic method may have beneficial analgesic effect on CNP after SCI with behavioral test and immunohistochemical test.

Dendritic Cell Activation by Glucan Isolated from Umbilicaria Esculenta

  • Kim, Hyung-Sook;Kim, Jee-Youn;Lee, Hong-Kyung;Kim, Moo-Sung;Lee, Sang-Rin;Kang, Jong-Soon;Kim, Hwan-Mook;Lee, Kyung-Ae;Hong, Jin-Tae;Kim, Young-Soo;Han, Sang-Bae
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.188-197
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    • 2010
  • Background: Lichen-derived glucans have been known to stimulate the functions of immune cells. However, immunostimulatory activity of glucan obtained from edible lichen, Umbilicaria esculenta, has not been reported. Thus we evaluated the phenotype and functional maturation of dendritic cells (DCs) following treatment of extracted glucan (PUE). Methods: The phenotypic and functional maturation of PUE-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. PUE-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity. Finally we detected the activation of MAPK and NF-${\kappa}B$ by immunoblot. Results: Phenotypic maturation of DCs was shown by the elevated expressions of CD40, CD80, CD86, and MHC class I/II molecules. Functional activation of DCs was proved by increased cytokine production of IL-12, IL-$1{\beta}$, TNF-${\alpha}$, and IFN-${\alpha}/{\beta}$, decreased endocytosis, and enhanced proliferation of allogenic T cells. Polymyxin B, specific inhibitor of lipopolysaccharide (LPS), did not affect PUE activity, which suggested that PUE was free of LPS contamination. As a mechanism of action, PUE increased phosphorylation of ERK, JNK, and p38 MAPKs, and enhanced nuclear translocation of NF-${\kappa}B$ p50/p65 in DCs. Conclusion: These results indicate that PUE induced DC maturation via MAPK and NF-${\kappa}B$ signaling pathways.

Protective Antitumor Activity through Dendritic Cell Immunization is Mediated by NK Cell as Well as CTL Activation

  • Kim, Kwang-Dong;Kim, Jin-Koo;Kim, Se-Jin;Choe, In-Seong;Chung, Tae-Hwa;Choe, Yong-Kyung;Lim, Jong-Seok
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.340-347
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    • 1999
  • Dendritic cells (DCs) are potent professional antigen-presenting cells (APC) capable of inducing the primary T cell response to antigen. Although tumor cells express target antigens, they are incapable of stimulating a tumor-specific immune response due to a defect in the costimulatory signal that is required for optimal activation of T cells. In this work, we describe a new approach using tumor-DC coculture to improve the antigen presenting capacity of tumor cells which does not require a source of tumor-associated antigen. Immunization of a weakly immunogenic and progressive tumor cocultured with none marrow-derived DCs generated an effective tumor vaccine. Immunization with the cocutured DCs was able to induce complete protectiv immunity against tumor challenges and was effective for the induction of tumor-specific CTL (cytotoxic T lymphocyte) activity. Furthermore, high NK cell activity was observed in mice in which tumors were rejected. In addition, immunization with tumor-pulsed DC s induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture of DCs with tumors generated antitumor immunity due to the NK cell activation as well as tumor-specific T cell. This approach would be used for designing tumor vaccines using DCs when the information about tumor antigens is limited.

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