• Title/Summary/Keyword: potential model

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The Optimal Activation State of Dendritic Cells for the Induction of Antitumor Immunity (항종양 면역반응 유도를 위한 수지상세포의 최적 활성화 조건)

  • Nam, Byung-Hyouk;Jo, Wool-Soon;Lee, Ki-Won;Oh, Su-Jung;Kang, Eun-Young;Choi, Yu-Jin;Do, Eun-Ju;Hong, Sook-Hee;Lim, Young-Jin;Kim, Ki-Uk;Jeong, Min-Ho
    • Journal of Life Science
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    • v.16 no.6
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    • pp.904-910
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    • 2006
  • Dendritic cells (DCs) are the only antigen presenting cells (APCs) capable of initiating immune responses, which is crucial for priming the specific cytotoxic T lymphocyte (CTL) response and tumor immunity. Upon activation by DCs, CD4+ helper T cells can cross-prime CD8+ CTLs via IL-12. However, recently activated DCs were described to prime in vitro strong T helper cell type 1 $(Th_1)$ responses, whereas at later time points, they preferentially prime $Th_2$ cells. Therfore, we examined in this study the optimum kinetic state of DCs activation impacted on in vivo priming of tumor-specific CTLs by using ovalbumin (OVA) tumor antigen model. Bone-marrow-derived DCs showed an appropriate expression of surface MHC and costimulatory molecules after 6 or 7-day differentiation. The 6-day differentiated DCs pulsed with OVA antigen for 8 h (8-h DC) and followed by restimulation with LPS for 24 h maintained high interleukin (IL)-12 production potential, accompanying the decreased level in their secretion by delayed re-exposure time to LPS. Furthermore, immunization with 8-h DC induced higher intracellular $interferon(IFN)-{\gamma}+/CD8+T$ cells and elicited more powerful cytotoxicity of splenocytes to EG7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with 24-h DC. In the animal study for the evaluation of therapeutic or protective antitumor immunity, immunization with 8-h DC induced an effective antitumor immunity against tumor of EG7 cells and completely protected mice from tumor formation and prolonged survival, respectively. The most commonly used and clinically applied DC-based vaccine is based on in vitro antigen loading for 24 h. However, our data indicated that antigen stimulation over 8 h decreased antitumor immunity with functional exhaustion of DCs, and that the 8-h DC would be an optimum activation state impacted on in vivo priming of tumor-specific CTLs and subsequently lead to induction of strong antitumor immunity.

Immunomodulatory Activity of Water Extract of Ulmus macrocarpa in Macrophages (유근피 추출물이 대식세포 면역조절에 미치는 영향)

  • Kwon, Da Hye;Kang, Hye-Joo;Choi, Yung Hyun;Chung, Kyung Tae;Lee, Jong Hwan;Kang, Kyung Hwa;Hyun, Sook Kyung;Kim, Byung Woo;Hwang, Hye Jin
    • Journal of Life Science
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    • v.26 no.1
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    • pp.50-58
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    • 2016
  • The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

Drug Interaction between Ginseng Extract (GE) and Sorafenib (쏘라페닙과 홍삼추출물간의 약물상호작용)

  • Lee, Nam-Hee;Park, Ho-Jae;Rho, Ja-Sung;Kim, Mi-Kyung;Lee, Yu-Kyoung;Cho, Eun-A;Heo, Jeong;Cho, Mong;Hwang, Tae-Ho
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1518-1525
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    • 2011
  • Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

Discrimination of Geographical Origin for Astragalus Root (Astragalus membranaceus) by Capillary Electrophoresis and Near-Infrared Spectroscopy (Capillary electrophoresis 및 근적외선분광분석기를 이용한 황기의 원산지 판별)

  • Kim, Eun-Young;Kim, Jung-Hyun;Lee, Nam-Yun;Kim, Soo-Jeong;Rhyu, Mee-Ra
    • Korean Journal of Food Science and Technology
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    • v.35 no.5
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    • pp.818-824
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    • 2003
  • Capillary electrophoresis (CE) and near-infrared spectroscopy (NIRS) were performed to discriminate astragalus roots (Astragalus membranaceus) according to geographical origin (domestic or foreign). Two-hundred-and-four astragalus roots were extracted with 30% methanol in 0.1 M phosphate buffer (pH 2.5) and separated in a uncoated fused-silica $(50\;{\mu}m{\times}27\;cm)$ capillary. Conditions for optimal analysis included: temperature $-45^{\circ}C$, voltage -14 kV, and pressure injection time -8 sec. The optimal separation buffer was 0.1 M phosphate buffer (pH 2.5) containing 40 mM hexane sulfonic acid with 20% 2-methoxy ethanol. Raw NIR spectra were obtained using NIRS, and modified partial least square regression was used to develop the prediction model. The correlation coefficient and standard error of prediction were 0.915 and 14.3%, respectively. Under the optimal conditions established for CE and NIRS, the geographical origins of the astragalus roots were correctly identified in 80 and 97%, respectively. Astragalus roots that were not discriminated by NIRS were correctly discriminated by CE. Hence, CE and NIRS are potential methods for discriminating the geographical origins of astragalus roots that complement one another.

The Modulation of Radiosensitivity by Combined Treatment of Selective COX-2 Inhibitor, NS 398 and EGF Receptor Blocker AG 1478 in HeLa Cell Line (선택적 COX-2 억제제 NS 398과 EGF 수용체 차단제 AG 1478의 복합투여가 HeLa 세포주의 방사선 감수성에 미치는 영향)

  • Youn Seon Min;Oh Young Kee;Kim Joo Heon;Park Mi Ja;Seong In Ock;Kang Kimun;Chai Gyuyong
    • Radiation Oncology Journal
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    • v.23 no.1
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    • pp.51-60
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    • 2005
  • Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

Antioxidative Effect and Neuraminidase Inhibitory Activity of Polyphenols Isolated from a New Korean Red Waxy Sorghum (Sorghum bicolor L. cv. Hwanggeumchalsusu) (황금찰수수(Sorghum bicolor L. cv. Hwanggeumchalsusu) 유래 에탄올 추출물 및 폴리페놀계 화합물의 항산화 활성 및 뉴라미니데이즈 억제 효과)

  • Ra, Ji-Eun;Seo, Kyung Hye;Ko, Jee Yeon;Lee, Mi-Ja;Kang, Hyeon Jung;Kim, Sun Lim;Chung, Ill-Min;Seo, Woo Duck
    • Journal of Life Science
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    • v.25 no.7
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    • pp.786-794
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    • 2015
  • To identify nutritional and therapeutic properties of the new Korean red waxy sorghum cultivar ‘Hwanggeumchalsusu (HGC)’, we assayed the antioxidative effects and neuraminidase inhibitory activity. A methanol and 70% ethanol extract of HGC exhibited strong antioxidative effects (IC50 values of 83.2±2.7 for DPPH) and 85.6±2.4 μg/ml for ABTS) and neuraminidase (ND) inhibitory activity (IC50 values of 1.8±0.1 from extracted with methanol and 3.4±0.1 μg/ml from extracted with 70% ethanol) compared with that of the control, noncolored sorghum cultivar ‘Huinchalsusu (HC)’ (IC50> 200 μg/ml). We isolated nine polyphenols, Gallic acid (1), Protocatecuic acid (2), p-Hydroxy benzoic acid (3), Vanillic acid (4), Caffeic acid (5), Ferulic acid (6), Luteolinidin (7), Apigeninidin (8), Luteolin (9), from the HGC - methanol extract, to determine whether they were the active components Luteolinidin of one kind of polyphenols from the HGC, exhibited significant antioxidative effects (IC50 values of 10.9±0.5 μM for DPPH and 8.6 0.6 μM for ABTS) and neuraminidase (ND) inhibitory activity (IC50 values of 26.3±0.6) showed noncompetitive inhibition model. The binding affinity of the ND inhibitors in molecular docking experiments correlated with their ND inhibitory activities. These results suggest that HGC may be utilized to serve as a potential effective antioxidant and inhibitor of ND.

Potentiation of Antitumor Effect of Radiotherapy by Recombinant Tumor Necrosis Factor-$\alpha$ (방사선의 항암작용에 대한 재조합 TNF-$\alpha$의 효과)

  • Seong Jinsil;Shin Hang Chul;Kim Gwi Eon;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.225-231
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    • 1998
  • Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

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Prognostic Factors for Local Control in Early Glottic Cancer Treated with Radiation Therapy (방사선치료를 받은 조기 성문암 환자의 국소 종양 제어에 관한 예후 인자)

  • Chung Woong-Ki;Ahn Sung Ja;Nam Taek Keun;Nah Byung Sik;Cho Jae-Shik;Lim Sang-Chull
    • Radiation Oncology Journal
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    • v.18 no.4
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    • pp.226-232
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    • 2000
  • Purpose :This study was performed to find out the prognostic factors affecting local control in early glottic cancer treated with radiation therapy alone. Materials and Methods :We analysed 37 patients of histologically confirmed early glottic cancer treated at Chonnam National University Hospital between July Im and December 1995, retrospectively. Age of patients ranged from 30 to 73 years (median; 59 years). Thirty-five (95$\%$) patients were male. Histological type was all squamous cell carcinoma. According to the staging system of 1997 American Joint Committee on Cancer, 37 patients were restaged as follows: Tla; U (73$\%$), Tlb; 3 (8$\%$), 72: 7 (19$\%$). Radiation therapy was done using 6 MV X-ray of linear accelerator The range of total radiation dose delivered to the glottic lesion was between 5,040 cGy and 7,020 cGy (median; 6,600 cGy). Median follow-up period was U months. local control rates were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of control rates between comparable groups. Multivariate analysis using Cox proportional hazard model was done to find out prognostic factors affecting local control. Results:5 year survival rate of 37 patients was 89$\%$. Local control rate of 37 patients was 74$\%$ in 5 years. We included age, 7-stage, anterior commissure involvement, fraction size, total radiation dose, treatment time of radiotherapy as potential prognostic factors in univariate and multivariate analysis. As a result, treatment time had statistical significance in local control rate in both univariate (p=0.026) and multivariate (p=0.017) analysis. Complication was not recorded except one patient with hypothyroidism. Conclusion :This study revealed that overall treatment time of radiation was a significant factor affecting local control rate.

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Effect of Phenolic Mediators and Humic Acid on the Removal of 1-Indanone Using Manganese Oxide (망간산화물(Birnessite)을 이용한 1- Indanone 제거 시 페놀계 반응매개체와 휴믹산(HA) 영향 평가)

  • Choi, Chan-Kyu;Eom, Won-Suk;Shin, Hyun-Sang
    • Journal of Korean Society of Environmental Engineers
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    • v.34 no.7
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    • pp.445-453
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    • 2012
  • An investigation for removal of 1-indanone (1-ID), which were commonly produced from the biological and/or chemical treatment and natural weathering of the PAHs-contaminated soils, via oxidative transformation mediated by birnessite in the presence of various phenolic mediators is described. This study also examines the potential effect of the natural occurring substance humic acid (HA) on the oxidative transformation. The experiment was carried out in aqueous phase as a batch test (10 mg/L 1-ID, 0.3 mM phenolic mediators, $1.0g/L\;{\delta}-MnO_2$, at pH 5). All of the 11 tested phenoilic mediators belong to the group of natural occurring phenols and are widely used as model constituents of humic substances. From the results of HPLC analysis, it is demonstrated that 1-ID was not reactive to birnessite itself, but it can be effectively removed in birnessite-mediated cross coupling reactions in the presence of the phenolic mediators. The percent removals of 1-ID after 2 day incubation were ranged from 9.2 to 71.2% depending on the phenolic mediators applied. The initial rate constant ($K_{int}$, $hr^{-1}$) values for the 1-ID removals obtained from the pseudo-first-order kinetic plots also widely ranged from 0.18 to 15.0. Results of the correlative analysis between the removal efficiencies and structural characteristics of phenolic mediators indicate that the transformation of the 1-ID was considerably enhanced by the addition of electron-donating substituents (e.g., -OH, $-OCH_3$) at the benzne ring, and much less enhanced by the addition of electron-withdrawing substituents (e.g., -COOH, -CHO). The presence of HA showed that removal efficiencies of 1-ID in the birnessite-phenolic mediator systems decreased with increasing HA concentrations. However at low concentration of HA (< 2 mg/L), it caused some enhancement in the removals of 1-ID as compared to the control.

Public Interest and Ownership Regulations in the Media Industry in the Era of Convergence Focused on Domestic Daily Newspapers' Ownership of Broadcasting Station (융합시대 미디어산업의 공익성과 소유규제 국내 종합일간지와 방송의 교차소유 문제를 중심으로)

  • Jun, Young-Beom
    • Korean journal of communication and information
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    • v.46
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    • pp.511-555
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    • 2009
  • Media-related regulations can be classified into two categories; regulations of individual media contents and regulations regarding the entry to and withdrawal from a certain field. In this dissertation, ownership regulations are regarded as legal and political measures so as to prevent the monopoly and oligopoly of public opinion, and to secure its diversity. Every country has its own regulation model according to its particular media environment. Korea too is obliged to actively respond to its environmental changes, at the same time vitalizing the media industry and protecting consumers' rights and interests. Strong political intentions to protect the public interest is necessary when it comes to media regulation policies, especially in the circumstances that public interest is an industrial priority. As the convergence of broadcasting and telecommunications is leading to a major shift in the media industry, the regulation of cross-media ownership is an issue involving potential conflicts among media-owners, non-governmental organizations and the authorities concerned, depending on their various viewpoints regarding the media industry. In this paper, an attempt was made to search necessity of redefining 'public interest', which is the logic behind the restriction of cross-media ownership, and to reconceptualize issues on the centralization and diversity of media. First, an examination of the actual conditions of newspaper companies was carried out in order to reinvestigate domestic cross-media ownership issues, which is represented by the cross-ownership issue of newspapers and broadcasting stations. Next, the dilemma of policies stimulated by the fusion of media was discussed based on cross-media ownership restrictions, and the need for efficient conflict control was suggested. Finally, proposals on the independency and public confidence of media-related policy-making authorities, the rationalization of regulation models, an itemized discussion on cross-media ownership regulation issues, the elaboration of measures for a balanced development among media were made. It could be found that a number of foreign countries were still facing challenges to prevent monopoly and oligopoly of the public opinion and the industry. A solution to settle disagreements about the dilemma of the media industry, including the cross-media ownership regulation issues, must be arranged on the grounds of 'mutual respect of public interest and industrial interest', In Korea, an ease on the ownership regulations adapting to the change in the media industry may be considered, however the softening of the cross-media ownership regulations must be approached with the utmost care. Paradoxically Relieving cross-media ownership regulations may be considered the foundation of a richer field of journalism, where there is no need for concern over the monopoly and oligopoly of public opinion.

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