Korean Abstract: 세계적으로 반무역자유화 정서가 확산되는 가운데 국제무역이 구조적으로 감소하고 있고 선진국을 중심으로 하는 복수국간협상이 확산되고 있다. 또한 파리기후변화협약의 이행으로 무역과 환경이 조화를 이루어야 하는 시대가 도래하였다. 본 보고서는 이러한 글로벌 통상환경에서 나타난 주요한 변화를 고려하여 나이로비 각료회의 이후 우리나라가 취해야 할 다자통상정책의 방향을 단기 DDA 협상대책과 중장기 정책방향으로 나누어 제시하였다. English Abstract: The WTO's Tenth Ministerial Conference, held in on December 2015, concluded with the adoption of the Nairobi Package, several ministerial decisions on agriculture, cotton and least-developed countries. The Package includes a historic decision to eliminate agricultural export subsidies, the most important reform of international trade rules in agriculture since the WTO was founded. The biggest disagreement among WTO members, however, goes beyond specific substantive issues: it is about the future of the Doha agenda and the WTO's negotiating function itself. While developing countries wished to continue with negotiations, industrialized nations, chief among them the United States, called for an end to the Doha Round. The Ministerial Declaration also acknowledges that WTO members different views on the future of the Doha Round negotiations but notes the strong commitment of all members to advance negotiations on the remaining Doha issues. In this situation, there have been significant changes in international trade since recent decades. First, trade growth has been anaemic since 2010. Already before the 2008 Global Crisis hit, the rate of growth of the ratio of global trade to GDP had slowed considerably. Most recent data show trade values declining. Second, plurilateral negotiations are rapidly widespread in the WTO. In particular, developed members have pushed for more sectoral deals like the ITA-II. Currently, a similar deal on tariff reductions for environmental goods is being negotiated. More sectoral tariff liberalization of this sort might be a good area to pursue. Along the same lines, the trade in services talks going on in Geneva could be brought formally into the WTO framework. Third, at the Paris climate conference (COP21) in December 2015, 195 countries adopted the first-ever universal, legally binding global climate deal, which is expected to affect a significant impact on global trade. At the heart of the Paris climate agreement are national-level plans, called Intended Nationally Determined Contributions (INDCs), to reduce greenhouse gas (GHG) emissions. Although these INDCs are voluntary, they are considered a critical first step for an agreement designed to progressively ratchet up national commitments to collectively limit a global temperature rise to 1.5 degrees Celsius above pre-industrial age levels. It is now time that we have to design a harmonization between trade and environments.
Alzheimer's disease (AD) is characterized by the deposition of aggregated beta-amyloid (Aβ), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of ER stress-mediated Aβ neurotoxicity still remain unknown. Here, we show that treatment of Aβ triggers the UPR in the SK-N-SH human neuroblastoma cells. Aβ mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2α pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Aβ neurotoxicity through reducing the activation of eIF2α and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2α pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Aβ treated neurons. These results indicate that PERK-eIF2α pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD.
RNA granules and exosomes produced by tumour cells under various stresses in the microenvironment act as critical determinants of cell survival by promoting angiogenesis, cancer metastasis, chemoresistance, and immunosuppression. Meanwhile, developmental cancer/testis (CT) antigens that are normally sequestered in male germ cells of the testes, but which are overexpressed in malignant tumour cells, can function as tumour antigens triggering immune responses. As CT antigens are potential vaccine candidates for use in cancer immunotherapy, they could be targeted together with crosstalk between stress granules, exosomes, and immune cells for a synergistic effect. In this review, we describe the effects of exosomes and exosomal components presented to the recipient cells under different types of stresses on immune cells and cancer progression. Furthermore, we discuss their significance for cancer immunity, as well as the outlook for their future application.
The aim of this study was to define immune-related triple negative breast cancer (TNBC) using immunohistochemistry for STAT1, CD20, CD3, IL-8, and IFN-γ and to assess its clinicopathologic characteristics.Tissues from 133 cases of TNBC were used for a tissue microarray. Expression of STAT1, CD20, CD3, IL-8, and IFN-γ were evaluated by immunohistochemical staining of the tissue microarrays. Immune-related type was defined as TNBC which was positive for STAT1 and negative for IL-8. A separate assessment of IL-8 and STAT1 status in tumor and stroma compartment was used to further classify immune-related type into tumor-based and stroma-based immune-related TNBC.Stroma-based, immune-related TNBC showed a significantly smaller central acellular zone (p=0.043), more lymphocytic infiltration (p⟨0.001), higher CD20 index (p=0.001), and higher CD3 index (p=0.018) than stroma-based, non-immune-related TNBC. IL-8 was independently associated with shorter disease-free survival (Hazard ratio: 3.804, 95% CI: 1.234-11.729, p=0.020) and shorter overall survival (Hazard ratio: 3.434, 95% CI: 1.132-10.414, p=0.029).Immune-related proteins such as STAT1, IFN-γ, IL-8, and CD20 were variably expressed in TNBCs. Stroma-based, immune-related TNBC (when positive for stromal STAT1 and negative for stromal IL-8) showed significantly higher lymphocytic infiltration including both CD3 positive T cell and CD20 positive B cell.
This study aimed to evaluate the association between hypertension management education and the adoption of multiple healthy behaviors.Cross-sectional study.Data from the 2019 Community Health Survey in Korea.Of the 213,900 participants in the 2019 database, 89,773 (42.0%) were hypertensive and 124,127 (58.0%) were normotensive.Secondary data analysis included a 1:1 computer-assisted personal interview. "Multiple healthy behaviors" included not smoking, not drinking excessively, and walking briskly. "Hypertension management education" referred to information on hypertension management that participants received from clinics, hospitals, and public health centers, outside consultation with a doctor.The association between hypertension management education and the adoption of multiple healthy behaviors was evaluated using multiple logistic regression.In total, 89,773 (42.0%) participants were hypertensive. Among 61,589 patients with diagnosed hypertension, only 7,719 (12.5%) received hypertension management education. Participants who received such education were more likely to adopt multiple healthy behaviors (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 1.21-1.34) than their counterparts (OR = 0.91, 95% CI: 0.89-0.93). Participants with undiagnosed hypertension were least likely to adopt multiple healthy behaviors (OR = 0.89, 95% CI: 0.86-0.92). No causal relationships were ascertained because of the cross-sectional study design.Education can improve the adoption of multiple healthy lifestyles among hypertensive patients. Patients should be encouraged to participate in hypertension management education.
The aim of study was to investigate the metabolism of tumor and stromal cells necessary to determine differential tumor-stroma metabolic interactions according to the molecular subtypes of triple-negative breast cancer (TNBC). Tissues from 132 patients of TNBC were prepared for use as tissue microarrays (TMA). Expression of CK5/6, EGFR, claudin 3, claudin 4, claudin7, E-cadherin, AR, GGT1, STAT1, and interleukin-8 was evaluated by immunohistochemical staining using TMA to classify molecular subtypes of TNBC. In addition, immunohistochemical staining for Glut1, CAIX, BNIP3, MCT4, Beclin-1, LC3A, LC3B, and p62 was performed. According to glycolytic status determined by the immunohistochemical expression of Glut-1 and CAIX in tumor and stroma, the metabolic phenotypes of the TNBCs were defined as follows: Warburg type (tumor: glycolysis, stroma: non-glycolysis), reverse Warburg type (tumor: non-glycolysis, stroma: glycolysis), mixed metabolic type (tumor: glycolysis, stroma: glycolysis), and metabolic null type (tumor: non-glycolysis, stroma: non-glycolysis). TNBCs were classified as follows: 79 Warburg type (59.8 %), 7 reverse Warburg type (5.3 %), 24 mixed metabolic type (18.2 %), and 22 metabolic null type (16.7 %). There was no statistical significance between the metabolic phenotypes and molecular subtypes (P=0.706). Reverse Warburg type showed the most dysfunctional mitochondrial status for stromal cells, while Warburg type showed the most functional mitochondrial status (P=0.036). Regarding stromal autophagy status, reverse Warburg type showed the most activated status, while all of the Warburg and metabolic null types showed a non-activated status (P<0.001). In conclusion, Warburg type was the most common metabolic phenotype in TNBC, while reverse Warburg type was the most unusual. Metabolic phenotypes did not differ among the molecular subtypes of TNBCs.
The purpose of this study is to investigate the expression of succinate dehydrogenase (SDH)A, SDHB, and HIF-1α in phyllodes tumors and the association with clinic-pathologic factors. Using tissue microarray (TMA) for 206 phyllodes tumor cases, we performed immunohistochemical stains for SDHA, SDHB, and HIF-1α and analyzed their expression in regard to clinicopathologic parameters of each case. The cases were comprised of 156 benign, 34 borderline, and 16 malignant phyllodes tumors. The expression of stromal SDHA and epithelial- and stromal- SDHB increased as the tumor progressed from benign to malignant (P⟨0.001). There were five stromal SDHA-negative cases and 31 stromal SDHB-negative cases. SDHB negativity was associated with a lower histologic grade (P=0.054) and lower stromal atypia (P=0.048). Univariate analysis revealed that a shorter disease free survival (DFS) was associated with stromal SDHB high-positivity (P=0.013) and a shorter overall survival (OS) was associated with high-positivity of stromal SDHA and SDHB (P⟨0.001 and P⟨0.001, respectively). The multivariate Cox analysis with the variables stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, stromal SDHA expression, and stromal SDHB expression revealed that stromal overgrowth was associated with a shorter DFS (hazard ratio: 24.78, 95% CI: 3.126-196.5, P=0.002) and a shorter OS (hazard ratio: 176.7, 95% CI: 8.466-3691, P=0.001). In conclusion, Tumor grade is positively correlated with SDHA and SDHB expression in the tumor stroma in phyllodes tumors of the breast. This result may be attributed to the increased metabolic demand in high grade tumors.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)