BACKGROUND: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. METHODS: B16F10 melanoma cells (5 x 10(4)/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. RESULTS: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: 2.667+/-0.184, 2.500+/-0.463, 2.000+/-0.286, 1.500+/-0.286, 1.667+/-0.297 for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-gamma secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate (2,643.3+/-5,89.7, 8,561.5+/-2,204.9. 6,901.2+/-141.1 pg/1 x 10(6) cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. CONCLUSION: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.
Animals ; Bone Marrow ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunotherapy ; Interleukin-4 ; Killer Cells, Natural ; Leukapheresis ; Melanoma* ; Mice ; Neoplasm Metastasis* ; Stem Cells

BACKGROUND: Tumor cell lysate has been considered as a preferential antigen source for the therapeutic dendritic cell pulsing. Our experiences with in vivo study with animal tumor model indicate the tumor cell lysate dependent differential effect of DC therapy. Our previous data show that MC38 lysate pulsed-DC induced stronger ag-specific immunity than CT26 lysate pulsed-DC in vitro. In this study we tried to reveal the mechanism for differential induction of ag-specific immunity of different colon cancer cell lysate pulsed-DCs. METHODS: MC38 and CT26 cell lines were prepared as lysate by freezing-thawing procedure. Tumor cell antigenicity was confirmed by detecting the surface expression of MHC I/II & B7.1/2 molecules. IL-10, IL-12 and TGF-beta in the tumor cell lysate were detected by ELISA and the presence of heat shock proteins were analysed by western blotting. RESULTS: The secretion of IL-10, a immune-inhibitory cytokine was about 470% higher in CT26 lysate than in MC38. Hsp 70 was detected only in the MC38 lysate but not in the CT26. On the other hand, Hsp 60 and 90 expression were not different in two colon cancer cell lysates. CONCLUSION: In two different colon caner cell lysate, immune inhibitory IL-10 (higher in CT26) and Hsp70 (MC38 superiority) were differentially expressed. These data indicate that higher ag- specific immunity induction by MC38 lysate pulsed-DC may due to the expression of hsp70 and lower secretion of IL-10, a immune-inhibitory cytokine than CT26 lysate. The significance of other cytokine and the surface marker expression will be discussed.
Animals ; Blotting, Western ; Cell Line ; Colon ; Colonic Neoplasms ; Dendritic Cells ; Enzyme-Linked Immunosorbent Assay ; Hand ; Heat-Shock Proteins ; Interleukin-10 ; Interleukin-12 ; Transforming Growth Factor beta

BACKGROUND: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary metastasis model. METHODS: B16F10 melanoma cells (1x10(5)/mouse) were inoculated intravenously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs (1x10(6)/mouse)[CGP1] were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. RESULTS: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: 2.7+/-0.3, 0.7+/-0.3 and 0.3+/-0.2 for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-gamma secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: 44.97+/-10.31, 1787.94+/-131.18, 1257.15+/-48.27, w/CloneM3 lysate: 0, 1591.13+/-1.83, 1460.47+/-86.05 pg/ml for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC (8.9+/-[CGP2]0.1, 11.6+/-0.8 and 12.6+/-0.7% specific NK activity for saline, B-DC and C-DC treated group, respectively). CONCLUSION: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.
Animals ; Bone Marrow ; Dendritic Cells* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Immunotherapy ; Interleukin-4 ; Killer Cells, Natural ; Lymphocytes ; Melanoma* ; Mice ; Neoplasm Metastasis*

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either CD34+ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-beta secretion were higher in SDC but CCR7 expression, IFN-gamma and IL-10 secretion were higher in MoDC. The proportion of CD11c+CD8a+ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-gamma secreting CD8+ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.
Animals ; Carcinoma, Lewis Lung ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Hematopoietic Stem Cells ; Interleukin-10 ; Interleukin-12 ; Interleukin-4 ; Lung ; Lung Neoplasms ; Mice ; Monocytes ; Peritoneum ; T-Lymphocytes ; Transforming Growth Factor beta ; Tumor Burden

In the present study, the frequency of research misconduct in Korean medical papers was analyzed using the similarity check software iThenticate®. All Korean papers written in English that were published in 2009 and 2014 in KoreaMed Synapse were identified. In total, 23,848 papers were extracted. 4,050 original articles of them were randomly selected for similarity analysis. The average Similarity Index of the 4,050 papers decreased over time, particularly in 2013: in 2009 and 2014, it was 10.15% and 5.62%, respectively. And 357 (8.8%) had a Similarity Index of ≥ 20%. Authors considered a Similarity Index of ≥ 20% as suspected research misconduct. It was found that iThenticate® cannot functionally process citations without double quotation marks. Papers with a Similarity Index of ≥ 20% were thus individually checked for detecting such text-matching errors to accurately identify papers with suspected research misconduct. After correcting text-matching errors, 142 (3.5% of the 4,050 papers) were suspected of research misconduct. The annual frequency of these papers decreased over time, particularly in 2013: in 2009 and 2014, it was 5.2% and 1.7%, respectively. The decrease was associated with the introduction of CrossCheck by KoreaMed and the frequent use of similarity check software. The majority (81%) had Similarity Indices between 20% and 40%. The fact suggested that low Similarity index does not necessarily mean low possibility of research misconduct. It should be noted that, although iThenticate® provides a fundamental basis for detecting research misconduct, the final judgment should be made by experts.
Duplicate Publication as Topic ; Editorial Policies ; Ethics* ; Judgment ; Periodicals as Topic ; Plagiarism ; Publications* ; Scientific Misconduct ; Synapses

OBJECTIVE: We developed a fully automated smartphone-based stress management application and explored its usability, potential feasibility, and preliminary efficacy for stress management in Korean employees. METHODS: Healthy employees working in large public enterprises were enrolled. Participants used our automated stress management application for four weeks. With the application, they monitored their stress level and life style factors. Personalized stress management techniques, including psychoeducation and cognitive behavioral technique, were also provided based on their stress level and lifestyle pattern. In 2014, additional relaxation techniques were incorporated. Participants’ mental health status and lifestyle pattern were self-assessed at baseline and at 4 weeks after using the application. RESULTS: A total of 68 subjects were recruited. The application generally received high satisfaction rating. After the intervention, perceived stress level was significantly decreased, both in 2013 and 2014 (BEPSI-K score pre. vs. post. 14.27 vs. 11.00, F=12.49, p=0.001 in 2013; 12.05 vs. 10.00, F=17.18, p < 0.001). In 2014, depression symptom severity was also significantly decreased (CES-D score pre- vs. Post-, 17.66 vs. 11.95, F=9.76, p=0.004). The effects were more significant in females and in those < 35 years. CONCLUSION: Our fully automated stress management application is acceptable and usable, showing preliminary efficacy for reducing employees’ stress levels.
Depression ; Female ; Humans ; Life Style ; Mental Health ; Public Sector ; Relaxation Therapy

Minor ginsenosides Rh1 and Rg2 were isolated from Korean red ginseng and reported to have various biological effects on anti-inflammatory and anti-stress activities. However, the effects of Rh1 and Rg2 on antioxidant activity and their regulatory effects on the antioxidant enzymes have not been studied. Since oxidative stress is one of the major toxic inflammatory responses stimulated by lipopolysaccharides (LPS), the present study investigated the role of minor ginsenosides Rh1 and Rg2 on antioxidant effects in LPS-treated RAW 264.7 cells. In this study, we found that treatment with ginsenosides Rh1 and Rg2 strongly inhibited LPS-stimulated intracellular ROS production in cells. Luciferase assay showed that treatment with LPS reduced antioxidant response element (ARE) encoding the pARE-luc promoter activity, while ginsenosides inhibited the pARE-luc promoter activity. Moreover, ginsenosides Rh1 and Rg2 exhibited anti-oxidative activity in LPS-induced cells by upregulating antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Our results suggest that minor ginsenosides Rh1 and Rg2 may be potential bio-active compounds for antioxidative effects by inhibiting the generation of ROS in RAW 264.7 cells.
Antioxidant Response Elements ; Antioxidants ; Catalase ; Ginsenosides* ; Glutathione Peroxidase ; Lipopolysaccharides ; Luciferases ; Oxidative Stress* ; Panax ; RAW 264.7 Cells* ; Reactive Oxygen Species ; Superoxide Dismutase

BACKGROUND: Dendritic cells (DCs) are increasingly being utilized for anti-cancer immunotherapy. Acute myeloid leukemia (AML) blasts are able to generate leukemia-derived DC. Advances in culture techniques and AML-DC characterization justify possible clinical applications. We investigated the ability of AML, acute lymphoblastic leukemia (ALL) and biphenotypic acute leukemia (BAL) blasts to differentiate into DCs in vitro and the qualified function of the leukemia-derived DCs. METHODS: Leukemia cells from 11 patients with AML, 3 patients with ALL and 2 patients with BAL were cultured with GM-CSF, IL-4 and with or without SCF. Cultured leukemia cells were evaluated by phenotype, mixed lymphocyte reaction (MLR), cytokine production and cytotoxic T cell (CTL) inducing activity. RESULTS: DCs were generated with GM-CSF and IL-4 from the leukemic blasts in 72% of the AML patient cells. MHC class I/II, CD11c and ICAM-1 were highly expressed in the AML-derived DCs. MLR and enzyme linked immunospot (ELISPOT) assays demonstrated that AML-DCs were able to induce T cell proliferation and activation into IFN-gamma secreting effector cells. The ALL blasts from two out of three patients differentiated into DCs with MHC class I/II+, CD11c+ only in the presence of GM-CSF, SCF and IL-4 for 14 days. CONCLUSION: These results suggest that functionallyactive DCs can be differentiated from AML blasts using GM-GSF and IL-4 and ALL, BAL blasts were differentiated into DCs only under stem cell-DC culture conditions.
Cell Proliferation ; Culture Techniques ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunotherapy ; Intercellular Adhesion Molecule-1 ; Interleukin-4 ; Leukemia* ; Leukemia, Biphenotypic, Acute ; Leukemia, Myeloid, Acute ; Lymphocyte Culture Test, Mixed ; Phenotype ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

In this article, it has been stated that this study was supported by SMtech Development Program (#2018-0006-01) and Research Fund of Chungnam National University (#2017-1794-01). This information has now been corrected as follows: This research was supported by Research Fund of Chungnam National University (#2017-1794-01).

Background: Uveitis is less common in children than in adults; however, pediatric uveitis has a relatively severe disease course that affects the quality of life. Although it is important to understand the epidemiological characteristics of pediatric uveitis, few studies have been conducted in large populations without referral bias. This study investigated the nationwide incidence and prevalence of pediatric uveitis in South Korea according to period, age, anatomic type, and systemic associations. Methods: This nationwide population-based cohort study used data from the Korean National Health Insurance Service from 2002 to 2018. This study included patients younger than 19 years of age with noninfectious uveitis with at least three claims of diagnostic codes of uveitis on separate days with at least once claim of prescription codes of steroid and immunosuppressive agents. All the cases were classified as anterior or non-anterior uveitis, and the overall incidence and prevalence were estimated by age, sex, and period. Patients with noninfectious uveitis were categorized by the presence of associated systemic conditions. Results: A total of 10,862,616 patients over 128,688,078 person-years were evaluated from 2005 to 2016. Overall, 5,368 cases of anterior uveitis and 604 cases of non-anterior uveitis were identified. The incidence and prevalence of pediatric noninfectious uveitis were 4.64 per 100,000 person-years (95% confidence interval [CI], 4.52–4.76) and 8.25 per 100,000 persons (95% CI, 8.09–8.41). Both the incidence and prevalence of pediatric uveitis increased with age. Anterior uveitis accounted for 84.7% of pediatric noninfectious uveitis prevalent cases (6.99 per 100,000 persons). Cases of juvenile idiopathic arthritis (JIA)-associated uveitis accounted for 8.7% (926 cases) of pediatric noninfectious uveitis cases with a prevalence of 0.72 per 100,000 (95% CI, 0.67–0.77). The proportion of systemic associations was higher and JIA-related uveitis accounted for 11.2% (803 cases) of recurrent or chronic noninfectious uveitis cases with a prevalence of 0.62 per 100,000. Conclusion This is the first population-based study investigating the largest population of pediatric patients with uveitis in Korea. The nationwide incidence and prevalence of pediatric noninfectious uveitis in 2005–2016 were 4.64 per 100,000 person-years and 8.25 per 100,000, respectively. The proportion of JIA in pediatric noninfectious uveitis was 8.7%.These population-based study findings provide a better understanding of the public health burden and aid in the planning of health-care strategies for pediatric patients with uveitis.