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Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice.
Yang, Hanseul,Lee, Sungsu,Lee, Seungjoo,Kim, Kangsan,Yang, Yeseul,Kim, Jeong Hoon,Adams, Ralf H,Wells, James M,Morrison, Sean J,Koh, Gou Young,Kim, Injune American Society for Clinical Investigation 2013 The Journal of clinical investigation Vol.123 No.1
<P>Little is known about the transcriptional regulation of tumor angiogenesis, and tumor ECs (tECs) remain poorly characterized. Here, we studied the expression pattern of the transcription factor Sox17 in the vasculature of murine and human tumors and investigated the function of Sox17 during tumor angiogenesis using Sox17 genetic mouse models. Sox17 was specifically expressed in tECs in a heterogeneous pattern; in particular, strong Sox17 expression distinguished tECs with high VEGFR2 expression. Whereas overexpression of Sox17 in tECs promoted tumor angiogenesis and vascular abnormalities, Sox17 deletion in tECs reduced tumor angiogenesis and normalized tumor vessels, inhibiting tumor growth. Tumor vessel normalization by Sox17 deletion was long lasting, improved anticancer drug delivery into tumors, and inhibited tumor metastasis. Sox17 promoted endothelial sprouting behavior and upregulated VEGFR2 expression in a cell-intrinsic manner. Moreover, Sox17 increased the percentage of tumor-associated CD11b+Gr-1+ myeloid cells within tumors. The vascular effects of Sox17 persisted throughout tumor growth. Interestingly, Sox17 expression specific to tECs was also observed in highly vascularized human glioblastoma samples. Our findings establish Sox17 as a key regulator of tumor angiogenesis and tumor progression.</P>
Kang, Sohi,Yang, Wonjun,Oh, Hanseul,Bae, Yeonji,Ahn, Meejung,Kang, Min Chul,Ko, Ryeo Kyeong,Kim, Gi Ok,Lee, Jun Hwa,Hyun, Jin Won,Moon, Changjong,Shin, Taekyun The Korean Society of Veterinary Science 2011 大韓獸醫學會誌 Vol.51 No.4
Several compounds and extracts isolated from a brown alga, Ishige (I.) okamurae, exhibit anti-oxidant and anti-inflammatory effects. The present study investigated whether the ethyl acetate (EtOAc) fraction of I. okamurae (EFIO) could ameliorate carbon tetrachloride ($CCl_{4}$)-induced hepatotoxicity in rats. Sprague-Dawley rats were intraperitoneally (i.p.) administered with EFIO at 10 or 50 mg/kg per day for 2 consecutive days before $CCl_{4}$ injection (3.3 mL/kg, i.p.). Twenty four hours later, the rats were anesthesized with diethyl ether and dissected. Pretreatment with EFIO significantly reduced the increased serum levels of alanine aminotransferase and aspartate aminotransferase in $CCl_{4}$-treated rats. Pretreatment with EFIO also significantly inhibited the reduced activities of superoxide dismutase and catalase in the $CCl_{4}$-injured liver. Histopathological evaluations showed that hemorrhage, hepatocyte necrosis, inflammatory cell infiltration, and fatty degeneration induced by $CCl_{4}$ treatment were ameliorated by the administration of EFIO. Additionally, liver immunohistochemical analyses revealed the marked reduction in ED1-positive monocyte-like macrophages in EFIO-pretreated rats given $CCl_{4}$. These results suggest that EFIO ameliorates $CCl_{4}$-induced liver injury, possibly through the inhibition of oxidative stress.
The evaluation of cost-of-illness due to use of cost-of-illness-based chemicals
Hong, Jiyeon,Lee, Yongjin,Lee, Geonwoo,Lee, Hanseul,Yang, Jiyeon The Korean Society of Environmental Toxicology 2015 환경독성보건학회지 Vol.30 No.-
Objectives This study is conducted to estimate the cost paid by the public suffering from disease possibly caused by chemical and to examine the effect on public health. Methods Cost-benefit analysis is an important factor in analysis and decision-making and is an important policy decision tool in many countries. Cost-of-illness (COI), a kind of scale-based analysis method, estimates the potential value lost as a result of illness as a monetary unit and calculates the cost in terms of direct, indirect and psychological costs. This study estimates direct medical costs, transportation fees for hospitalization and outpatient treatment, and nursing fees through a number of patients suffering from disease caused by chemicals in order to analyze COI, taking into account the cost of productivity loss as an indirect cost. Results The total yearly cost of the diseases studied in 2012 is calculated as 77 million Korean won (KRW) per person. The direct and indirect costs being 52 million KRW and 23 million KRW, respectively. Within the total cost of illness, mental and behavioral disability costs amounted to 16 million KRW, relevant blood immunological parameters costs were 7.4 million KRW, and disease of the nervous system costs were 6.7 million KRW. Conclusions This study reports on a survey conducted by experts regarding diseases possibly caused by chemicals and estimates the cost for the general public. The results can be used to formulate a basic report for a social-economic evaluation of the permitted use of chemicals and limits of usage.
Notch Pathway Targets Proangiogenic Regulator Sox17 to Restrict Angiogenesis
Lee, Seung-Hun,Lee, Sungsu,Yang, Hanseul,Song, Sukhyun,Kim, Kangsan,Saunders, Thomas L.,Yoon, Jeong K.,Koh, Gou Young,Kim, Injune American Heart Association, Inc. 2014 Circulation research Vol.115 No.2
<P><B><U>Rationale</U>:</B></P><P>The Notch pathway stabilizes sprouting angiogenesis by favoring stalk cells over tip cells at the vascular front. Because tip and stalk cells have different properties in morphology and function, their transcriptional regulation remains to be distinguished. Transcription factor Sox17 is specifically expressed in endothelial cells, but its expression and role at the vascular front remain largely unknown.</P><P><B><U>Objective</U>:</B></P><P>To specify the role of Sox17 and its relationship with the Notch pathway in sprouting angiogenesis.</P><P><B><U>Methods and Results</U>:</B></P><P>Endothelial-specific <I>Sox17</I> deletion reduces sprouting angiogenesis in mouse embryonic and postnatal vascular development, whereas <I>Sox17</I> overexpression increases it. Sox17 promotes endothelial migration by destabilizing endothelial junctions and rearranging cytoskeletal structure and upregulates expression of several genes preferentially expressed in tip cells. Interestingly, Sox17 expression is suppressed in stalk cells in which Notch signaling is relatively high. Notch activation by overexpressing Notch intracellular domain reduces Sox17 expression both in primary endothelial cells and in retinal angiogenesis, whereas Notch inhibition by delta-like ligand 4 (Dll4) blockade increases it. The Notch pathway regulates Sox17 expression mainly at the post-transcriptional level. Furthermore, endothelial <I>Sox17</I> ablation rescues vascular network from excessive tip cell formation and hyperbranching under Notch inhibition in developmental and tumor angiogenesis.</P><P><B><U>Conclusions</U>:</B></P><P>Our findings demonstrate that the Notch pathway restricts sprouting angiogenesis by reducing the expression of proangiogenic regulator Sox17.</P>
Kataru, Raghu P.,Jung, Keehoon,Jang, Cholsoon,Yang, Hanseul,Schwendener, Reto A.,Baik, Jung Eun,Han, Seung Hyun,Alitalo, Kari,Koh, Gou Young American Society of Hematology 2009 Blood Vol.113 No.22
<P>Using a bacterial pathogen-induced acute inflammation model in the skin, we defined the roles of local lymphatic vessels and draining lymph nodes (DLNs) in antigen clearance and inflammation resolution. At the peak day of inflammation, robust expansion of lymphatic vessels and profound infiltration of CD11b+/Gr-1+ macrophages into the inflamed skin and DLN were observed. Moreover, lymph flow and inflammatory cell migration from the inflamed skin to DLNs were enhanced. Concomitantly, the expression of lymphangiogenic growth factors such as vascular endothelial growth factor C (VEGF-C), VEGF-D, and VEGF-A were significantly up-regulated in the inflamed skin, DLNs, and particularly in enriched CD11b+ macrophages from the DLNs. Depletion of macrophages, or blockade of VEGF-C/D or VEGF-A, largely attenuated these phenomena, and produced notably delayed antigen clearance and inflammation resolution. Conversely, keratin 14 (K14)-VEGF-C transgenic mice, which have dense and enlarged lymphatic vessels in the skin dermis, exhibited accelerated migration of inflammatory cells from the inflamed skin to the DLNs and faster antigen clearance and inflammation resolution. Taken together, these results indicate that VEGF-C, -D, and -A derived from the CD11b+/Gr-1+ macrophages and local inflamed tissues play a critical role in promoting antigen clearance and inflammation resolution.</P>
Value of a statistical life estimation of carcinogenic chemicals for socioeconomic analysis in Korea
Lee, Geonwoo,Lee, Yongjin,Lee, Hanseul,Hong, Jiyeon,Yang, Jiyeon The Korean Society of Environmental Toxicology 2015 환경독성보건학회지 Vol.30 No.-
Objectives To protect public health from risk, the Minister of Environment in Korea legislated an act concerning the registration and evaluation of chemical substances. In this study, we estimated the value of a statistical life (VSL) of carcinogenic chemicals to evaluate the socioeconomic analysis in Korea. Methods The estimation of the health benefit can be calculated through an individual's VSL and willingness to pay (WTP). To estimate the VSL and WTP, we used a contingent valuation method through a web-based survey. Results The survey is conducted with 1434 people living in Seoul and six large cities. An analysis of the survey is essential to review the distribution of the characteristics of the target population. The statistically significant variables affecting the WTP are location, age, household income, quality of life. Through the review of data, we secured statistical validity. The WTP was estimated as 41205 Korean won (KRW)/person, and the estimated VSL appeared as 796 million KRW/person. Conclusions There is a case in which the amount of statistical life value is estimated in connection with domestic environmental policy, fine dust, etc. However, there are no cases of evaluation for chemical. The utilization of this result is possible for conducting other study with chemicals.
The evaluation of cost-of-illness due to use of cost-of-illness-based chemicals
양지연,Yongjin Lee,Geonwoo Lee,Hanseul Lee,Jiyeon Yang 환경독성보건학회 2015 환경독성보건학회지 Vol.30 No.-
Objectives This study is conducted to estimate the cost paid by the public suffering from disease possibly caused by chemical and to examine the effect on public health. Methods Cost-benefit analysis is an important factor in analysis and decision-making and is an important policy decision tool in many countries. Cost-of-illness (COI), a kind of scale-based analysis method, estimates the potential value lost as a result of illness as a monetary unit and calculates the cost in terms of direct, indirect and psychological costs. This study estimates direct medical costs, transportation fees for hospitalization and outpatient treatment, and nursing fees through a number of patients suffering from disease caused by chemicals in order to analyze COI, taking into account the cost of productivity loss as an indirect cost. Results The total yearly cost of the diseases studied in 2012 is calculated as 77 million Korean won (KRW) per person. The direct and indirect costs being 52 million KRW and 23 million KRW, respectively. Within the total cost of illness, mental and behavioral disability costs amounted to 16 million KRW, relevant blood immunological parameters costs were 7.4 million KRW, and disease of the nervous system costs were 6.7 million KRW. Conclusions This study reports on a survey conducted by experts regarding diseases possibly caused by chemicals and estimates the cost for the general public. The results can be used to formulate a basic report for a social-economic evaluation of the permitted use of chemicals and limits of usage.