SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways

Zhang, Yan-Li,Li, Qing,Yang, Xiao-Mei,Fang, Fang,Li, Jun,Wang, Ya-Hui,Yang, Qin,Zhu, Lei,Nie, Hui-Zhen,Zhang, Xue-Li,Feng, Ming-Xuan,Jiang, Shu-Heng,Tian, Guang-Ang,Hu, Li-Peng,Lee, Ho-Young,Lee, Su-J American Association for Cancer Research 2018 Cancer research Vol.78 No.9

<P>Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P>Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.</P><P><B>Significance:</B> Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P><B>Graphical Abstract:</B> http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. <I>Cancer Res; 78(9); 2305–17. ©2018 AACR</I>.</P><P><B>Graphical Abstract</B></P><P> [Figure]</P>

The Crucial Role of the Establishment of Computed Tomography Density Conversion Tables for Treating Brain or Head/Neck Tumors

Yang, Shu-Chin,Lo, Su-Hua,Shie, Li-Tsuen,Lee, Sung-Wei,Ho, Sheng-Yow Korean Society of Medical Physics 2021 의학물리 Vol.32 No.3

Purpose: The relationship between computed tomography (CT) number and electron density (ED) has been investigated in previous studies. However, the role of these measures for guiding cancer treatment remains unclear. Methods: The CT number was plotted against ED for different imaging protocols. The CT number was imported into ED tables for the Pinnacle treatment planning system (TPS) and was used to determine the effect on dose calculations. Conversion tables for radiation dose calculations were generated and subsequently monitored using a dosimeter to determine the effect of different CT scanning protocols and treatment sites. These tables were used to retrospectively recalculate the radiation therapy plans for 41 patients after an incorrect scanning protocol was inadvertently used. The gamma index was further used to assess the dose distribution, percentage dose difference (DD), and distance-to-agreement (DTA). Results: For densities <1.1 g/cm³, the standard deviation of the CT number was ±0.6% and the greatest variation was noted for brain protocol conditions. For densities >1.1 g/cm³, the standard deviation of the CT number was ±21.2% and the greatest variation occurred for the tube voltage and head and neck (H&N) protocol conditions. These findings suggest that the factors most affecting the CT number are the tube voltage and treatment site (brain and H&N). Gamma index analyses for the 41 retrospective clinical cases, as well as brain metastases and H&N tumors, showed gamma passing rates >90% and <90% for the passing criterion of 2%/2 and 1%/1 mm, respectively. Conclusions: The CT protocol should be carefully decided for TPS. The correct protocol should be used for the corresponding TPS based on the treatment site because this especially affects the dose distribution for brain metastases and H&N tumor recognition. Such steps could help reduce systematic errors.

Histopathological Evidence for the Existence of Primary Liver Progenitor Cell Cancer: Insight from Cancer Stem Cell Pathobiology

( Cheng-maw Ho ),( Shu-li Ho ),( Chia-tung Shun ),( Po-huang Lee ),( Ya-hui Chen ),( Chin-sung Chien ),( Hui-ling Chen ),( Rey-heng Hu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Primary liver progenitor cell cancer is a rare disease entity without definite evidence and characterization. Current nomenclature of primary liver cancer with prominent progenitor features is not comprehensive. This study was aimed to investigate the existence of this kind of primary liver cancer and characterize it immunohistopathologically based on the emerging understanding of cancer stem cell pathobiology. Methods: Surgical specimens from primary liver cancer which posed diagnostic difficulty fitting within current WHO classification of combined hepatocellular-cholangiocellular carcinoma with stem-cell features according to the growth morphology and its suggested immunohistochemical features, were stained with antibodies against well-defined markers of progenitor cells, stemness, and differentiation toward hepatocytes or cholangiocytes. Comparative interpretation of images was processed considering the histological morphology and characteristic markers. Results: The primary liver cancer consisted of CD24+ cancer progenitor cells and CD90+ mesenchymal stromal cells, which were intimately mixed. CD24+ cancer cells demonstrated bi-directional trends of differentiation: bile ductule transformation (cytokeratin 19+, epithelial cell adhesion molecule [EpCAM]+, neural cell adhesion molecule [NCAM]+, CD133+, and delta-like 1 homolog [DLK1]+); and trabecular or nested cell clusters toward hepatic lineage (hepatocyte nuclear factor-4 alpha [HNF-4α]+, Hep Par1+ and negative for CK19, EpCAM, CD133, and DLK1). Moderate lymphocyte (mostly CD4+ and CD8+ T cells) infiltrated in the CD90+ cancer- associated stroma. Conclusions: We provided the corroboration that liver progenitor cells can form primary liver cancer, not just presented as few side population of cancer stem cells. Its existence might pose significance for future stem cell therapeutic intervention targeting liver diseases, albeit the disease is rare.

Hepatocyte and mesenchymal stem cell co-transplantation in rats with acute liver failure

Cheng-Maw Ho,Ya-Hui Chen,Chin-Sung Chien,Shu-Li Ho,Hui-Ling Chen,Rey-Heng Hu,Po-Huang Lee 대한이식학회 2020 Korean Journal of Transplantation Vol.34 No.2

Background: Cell therapy is considered a potential alternative to liver transplantation in acute liver failure (ALF). We aimed to evaluate the add-on therapeutic benefit of hepatocyte and mesenchymal stem cell (MSC) cotransplantation over hepatocyte-only transplantations in a rat model of ALF. Methods: ALF was induced by D-galactosamine in Sprague-Dawley rats. Freshly isolated donor hepatocytes were derived from Tg (UBC-emGFP) rats and MSCs were collected from the bone marrow cells of DsRed rats. Donor hepatocytes (1×107/mL) were intraportally transplanted 24 hours after treatment with D-galactosamine over a 70-second interval, and donor MSCs (0.5, 1, or 2×106/0.5 mL) were intraportally transplanted 1 hour after the hepatocyte transplantation was complete. Animals were sacrificed after 7 and 14 days and subjected to donor cell identification, liver histology, serologic testing, and immunohistopathological examination. Results: MSCs were observed in the periportal area, 1 and 2 weeks after transplantation. Transplanted hepatocytes did not actively proliferate when compared to hepatocyte-only transplantation. Morphologically, transplanted MSCs did not appear to differentiate into hepatocytes even 2 weeks after transplantation. Cotransplantation of MSCs was associated with lower macrophage infiltration, and reduced type I collagen, hepatocyte growth factor, tumor necrosis factor-α, and interleukin 10 expression, with similar gene expression profiles for epidermal growth factor and interleukin 6, when compared to hepatocyte-only transplantation. Conclusions: Hepatocyte and MSC cotransplantation is feasible and safe in rat models of ALF. MSCs were found to survive the process and could be located within the periportal niches 2 weeks after treatment, without enhancing transplanted hepatocyte proliferation or differentiating into hepatocytes, while ameliorating the inflammatory response.

Relationship Between Career Self-Efficacy and Nursing Competencies among Baccalaureate Nursing Graduates

Ming-Yueh Tseng,Shiow-Li Hwang,Mei-Yao Ho,Wei-Shu Lai,Yu-Jue Hong 한국간호과학회 2015 한국간호과학회 학술대회 Vol.2015 No.10

The Effect of a Scenario-Based Spiritual Care Course on Spiritual Care Competence among Clinical Nurses

Suh-Ing Hsieh,Li-Ling Hsu,Hui-Ling Lin,Chen-Yi Kao,Yi-Ping Tseng,Li-Yun Szu,Ching-Yun Lee,Lun-Hui Ho,Shu-Ling Yeh,Shu-Hua Kao,Yen-Fang Chou,Tzu-Hsin Huang 한국성인간호학회 2021 성인간호학회 학술대회 Vol.2021 No.8

상사-부하 교환관계가 조직시민행동에 미치는 영향: 심리적 임파워먼트와 무형식 학습의 이중매개효과

하선숙(He, Shan-Shu),이의연(Li, Yi-Ran),전정호(Jeon, Jeong-Ho) 한국산업경제학회 2020 산업경제연구 Vol.33 No.6

4차 산업혁명이 도래하면서, 기업들도 기존의 획일적 정책 부분에서 탈피하여 지속가능한 경영 및 혁신을 위해 다양한 노력을 기울이고 있다. 따라서 본 연구는 이러한 변화무쌍한 경영환경을 고려하여, LMX가 심리적 임파워먼트, 무형식 학습, 그리고 조직시민행동에 미치는 영향과 심리적 임파워먼트와 무형식 학습의 이중매개효과를 실증·분석하였다. 연구목적을 달성하기 위해 수도권에 소재한 대기업에 재직하고 있는 구성원 325명의 응답을 표본으로 SPSS 27.0, Amos 27.0을 이용하여 분석하였다. 연구결과, 첫째, LMX는 조직시민행동에 정(+)의 영향을 미치는 것으로 나타났다. 둘째, 심리적 임파워먼트와 무형식학습은 LMX와 조직시민행동의 관계에서 매개역할을 하는 것으로 나타났다. 셋째, LMX와 조직시민행동의 관계에서 심리적 임파워먼트와 무형식 학습은 이중 매개역할을 하는 것으로 나타났다. 시사점은 다음과 같다. 이론적 시사점은 본 연구를 통해 선행연구에서 제시된 LMX의 효과를 재확인하고, LMX가 사회교환관계를 통해 이론적 확장에 기여하였다. 실무적 시사점은 본 연구결과를 통해 실제 기업에서 조직의 목표를 효율적이고 효과적으로 달성하는 데 구성원들의 조직시민행동이 필요하고, 이를 강화시키는 방안을 시사하였다. The purpose of this study is to examine the impact of leader-member exchange on psychological empowerment, informal learning, and organizational citizenship behavior and to analyze the dual mediation effect of psychological empowerment and informal learning. The authors used 325 questionnaires collected by members in domestic companies. The results showed that leader-member exchange has no positive effect on organizational citizenship behavior. We found also that psychological empowerment and informal learning mediates the effect of leader-member exchange on organizational citizenship behavior, respectively. Furthermore, in the relationship between leader-member exchange and organizational citizenship behavior, psychological empowerment and informal learning play a dual mediating role. Present paper contributes to theoretical expansion by explaining that these behavior patterns are identified by social exchange theory. The practical implication is that this study confirmed that members in the actual management field are willing to perform organizational citizenship behavior in order to achieve the organization’s goal efficiently and effectively.

구성원들의 조직시민행동을 어떻게 높이는가? : 그릿의 매개효과

하선숙(He, Shan-Shu),전정호(Jeon, Jeong-Ho),이의연(Li, Yi-Ran) 한국산업경제학회 2021 산업경제연구 Vol.34 No.5

본 연구에서는 구성원들의 조직시민행동을 지속적으로 높이기 위하여, 일의 의미, 육성적 피드백, 그릿의 구조적 인과관계를 파악하고 SmartPLS의 구조방정식 모형을 이용하여 검증하였다. 이러한 목적을 달성하기 위해 2021년 7월 15일부터 2021년 7월 20일까지 예비조사를 실시하여, 설문지의 오류와 미흡한 부분을 수정하였다. 설문지의 2차 배포 및 회수는 Amazon Mechanical Turk의 온라인 설문을 사용하여 2021년 7월 23일부터 2021년 7월 26일까지 설문조사를 실시하였고, 309부를 최종분석에 사용되었다. 연구결과, 일의 의미와 육성적 피드백이 그릿을 매개로 조직시민행동에 유의한 영향을 미치는 것으로 나타났다. 이론적 시사점은 본 연구를 통해 선행연구에서 제시된 일의 의미와 육성적 피드백의 효과를 재확인하고, 일의 의미와 육성적 피드백이 사회정체성이론과 사회교환이론을 통해 그릿을 매개로 조직시민행동에 미치는 영향을 실증 · 분석하였다는 데 이론적 함의를 가진다. 실무적 시사점은 본 연구결과를 통해 기업에서 구성원들이 업무를 완수하는 과정에서 조직시민행동이 중요하지만, 일의 의미와 육성적 피드백, 그릿에 의해 지속적 조직시민행동이 가능함을 밝히는 데 의의가 있다. This study assessed and validated the causative structural relationships among the meaning of work, developmental feedback, and grit to influence members’ organizational citizenship behavior, using the structural equation model of SmartPLS. To achieve this purpose, this study corrected errors in questionnaires and inadequate parts by conducting a preliminary survey from July 15 through 20, 2021. For the secondary distribution and collection of questionnaires, a survey was conducted, using an online survey of Amazon Mechanical Turk from July 23 through 26, 2021, and 309 copies were used in the final analysis. The findings of this study demonstrated that the meaning of work and developmental feedback had significant impacts on organizational citizenship behavior using grit as a medium. This study has theoretical implications in that it re-validated the meaning of work and the effect of developmental feedback presented in the preceding studies and that it demonstrated and analyzed the impact on organizational citizenship behavior using grit as a medium through, the meaning of work and developmental feedback. As for a practical implication, the findings of this study demonstrated that organizational citizenship behavior is important in the process in which the members of enterprises complete tasks, but more importantly, this study is significant in that it reveals that continuous organizational citizenship behavior is possible by the meaning of work, developmental feedback, and grit.

Benzodiazepine-Associated Carcinogenesis

Shih-Chieh Ku,Pei-Shen Ho,Yu-Ting Tseng,Ta-Chuan Yeh,Shu-Li Cheng,Chih-Sung Liang 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.9

Objective Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. Methods A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. Results Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. Conclusion Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.

한-튀르키예의 무역관습과 무역 확대 방안

박광서(Kwang-So PARK),도광호(Kwang-Ho DHO),이홍숙(Hong-Shu LI) 한국무역상무학회 2023 貿易商務硏究 Vol.98 No.-

한국과 튀르키예는 수출입 규모와 순위 면에서 아직은 만족할 만한 수준은 아니지만, 튀르키예는 정치ㆍ경제ㆍ지정학적으로 중요한 국가이고 무역관점에서도 발전 가능성이 많은 국가이다. 본 논문은 튀르키예의 무역 및 통상현황을 살펴봄으로써 한국기업의 對 튀르키예 진출을 확대하려는 바람에서 다음과 같이 3부분으로 살펴보았다. 우선, 튀르키예에 대한 기본 이해를 바탕으로 무역 및 통상현황을 살펴봄으로써 수출시장으로써 튀르키예의 중요성과 우리나라와의 관계를 개괄적으로 살펴본다. 둘째, 한-튀르키예의 인코텀스, 무역결제, 무역운송 등 무역관습 활용현황과 시사점을 살펴보았다. 마지막으로 한-튀르키예의 무역 발전을 위한 여러 가지 제언을 담았다. Korea and Turkiye are not yet at a satisfactory level in terms of the scale and ranking of imports and exports, but Turkiye is an important country politically, economically, and geopolitically, and has great potential for development in terms of trade. Therefore, this paper researched to help Korean companies increase their entry into Turkiye by examining the trade status, strategies, and trade customs of Turkiye. As a result of examining trade customswith Turkiye. FOBand CIF aremainly used as contract conditions, and the proportion of letters of credit in terms of payment is relatively high. In addition, since both countries are peninsular countries in terms of transportation, sea transportation is mainly used. Also several suggestions for the development of Korea-Turkiye trade were proposed. First of all, there aremany differences in religion and culture betweenKorea and Turkiye, so they have formed different business practices. Therefore, it is necessary to build trade relationships and trust based on an understanding of the business customs of Turkiye. Next, in order to expand exports to Turkiye, a ‘multi-track strategy’ is needed, such as ①expansion of trade targets from commodity trade to service trade,②participation of an unspecified number of traders, and③increase in contract amount per unit. Lastly, both countries need to actively utilize the FTAthat has been in effect since 2013 by discovering trade products that are competitivewith each other,while strengthening cooperation in the service sector between the two countries by utilizing the FTA Service Investment Agreement that has been in effect since 2018.