SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling

Kim, Kangsan,Kim, Il-Kug,Yang, Jee Myung,Lee, Eunhyeong,Koh, Bong Ihn,Song, Sukhyun,Park, Junseong,Lee, Sungsu,Choi, Chulhee,Kim, Jin Woo,Kubota, Yoshiaki,Koh, Gou Young,Kim, Injune Grune & Stratton 2016 Circulation research Vol.119 No.7

<P>Rationale: Vascular endothelial growth factor (VEGF) signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Although the Notch pathway-mediated suppression of excessive VEGF activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Transcription factor Sox17 is indispensable for angiogenesis, but its association with VEGF signaling is largely unknown. The contribution of other Sox members to angiogenesis also remains to be determined. Objective: To reveal the genetic interaction of Sox7, another Sox member, with Sox17 in developmental angiogenesis and their functional relationship with VEGF signaling. Methods and Results: Sox7 is expressed specifically in endothelial cells and its global and endothelial-specific deletion resulted in embryonic lethality with severely impaired angiogenesis in mice, substantially overlapping with Sox17 in both expression and function. Interestingly, compound heterozygosity for Sox7 and Sox17 phenocopied vascular defects of Sox7 or Sox17 homozygous knockout, indicating that the genetic cooperation of Sox7 and Sox17 is sensitive to their combined gene dosage. VEGF signaling upregulated both Sox7 and Sox17 expression in angiogenesis via mTOR pathway. Furthermore, Sox7 and Sox17 promoted VEGFR2 (VEGF receptor 2) expression in angiogenic vessels, suggesting a positive feedback loop between VEGF signaling and SoxF. Conclusions: Our findings demonstrate that SoxF transcription factors are indispensable players in developmental angiogenesis by acting as positive feedback regulators of VEGF signaling.</P>

A Significant Number of Sessile Serrated Adenomas Might Not Be Accurately Diagnosed in Daily Practice

( Soo Woong Kim ),( Jae Myung Cha ),( Joung Il Lee ),( Kwang Ro Joo ),( Hyun Phil Shin ),( Gou Young Kim ),( Sung Jig Lim ) 대한소화기기능성질환·운동학회 2010 Gut and Liver Vol.4 No.4

Background/Aims: The diagnosis of hyperplastic polyps (HPs) may involve a conglomeration of subgroups of serrated polyps. The diagnosis of HPs may therefore be revisited if this is sessile serrated adenoma (SSA). The aim of this study was to determine clinically and endoscopically relevant information associated with reclassification to SSA. Methods: After reviewing the data from 1,372 patients who underwent colonoscopic polypectomy, 49 HPs larger than 10 mm were analyzed in this study. Two gastrointestinal pathologists reclassified each of the original 49 HPs as conventional HPs, SSAs, and others. Results: Among the 49 initially diagnosed HPs, 18.4% were reclassified into SSAs or mixed polyps. Overall architectural features were useful for the diagnosis of SSA, but cytological features were less useful. The patient and polyp characteristics did not differ between HPs with and without reclassification of the initial pathological diagnosis. Conclusions: A significant number of SSAs might not be accurately diagnosed in daily clinical practice without any predilection for size, shape, and location. Therefore, when large HPs are diagnosed in clinical practice, it is necessary for physicians to have greater awareness of the diagnosis of SSA and to individualize subsequent surveillance. (Gut Liver 2010;4:498-502)

공공기관의 균형성과표 관점간 구조적 관계에 관한 실증적 연구 : 국세청 성과를 중심으로

임병규(Lim Beung-Gou),김명희(Kim Myung-Hee),김준호(Kim Jun-Ho) 한국국제회계학회 2009 국제회계연구 Vol.0 No.28

본 연구에서는 공공기관 즉, 국세청에 BSC를 적용함에 있어서 5가지의 관점간(학습과 성장, 혁신 및 운영, 업무절차, 정책집행, 이해관계자)의 인과관계를 파악함으로써 BSC가 공공기관에서의 성과평가 시스템으로서의 적합성이 있는지를 검증해 보고자 하였다. 분석의 결과 학습과 성장은 혁신 및 운영, 업무절차와 인과관계가 있는 것으로 나타났으나, 학습과 성장은 정책집행에 영향을 미치지 않는 것으로 나타났다. 혁신 및 운영은 업무절차와 정책집행과 각각 인과관계가 있는 것으로 나타났다. 그리고 업무절차는 정책집행과 이해관계자와 각각 인과관계가 있는 것으로 나타났다. 마지막으로 정책집행이 이해관계자와 인과관계가 있는 것으로 나타났다. 본 연구에서 나온 결과와 향후에 국세청을 대상으로 다시 한번 연구를 조사를 실시하여 나온 결과를 비교하여, 즉, 시계열적 분석을 행함으로써 BSC 관점간의 인과관계가 어떠한 변화를 일으키는지에 대해서도 연구하면 좋을 것이다. The present study was aimed at analyzing the causal relationship among the five perspectives(interest group, execution of policy, business process, renovation and operation, and learning and growth) as stated above by applying BSC to such public organization as NTS, with a view to explore if BSC might be an optimal system to evaluate the performance of public organizations as a whole. From the analysis, learning and growth turned out to have causal relationship with renovation and operation as well as with business process, while they had little influence upon execution of policy. Renovation and operation were found to have no causal relationship with business process and execution of policy, respectively. It was shown that the business process maintained causal relationship with execution of policy and interest group each. Finally, it became evident that execution of policy had causal relationship with interest group. It is therefore suggested to conduct further researches on NTS and to compare their outcomes with the findings of this study in a time-serial manner in a bid to determine how the causal relationship among perspectives might have changed.

효율적인 의약품 평가를 위한 약물계량학 분석법 도입의 전략 방안

( Sang Min Lee ),( Boyoon Choi ),( Hwi Yeol Yun ),( Da Hae Jun ),( Myung Gou Kim ),( Ji Hye Ha ),( Young Hoon Kim ),( Eun Hee Ji ),( Won Ku Kang ),( Na Young Han ),( Wan Gyoon Shin ),( Jung Mi Oh ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0

Over the past few decades, drug regulatory agencies in advanced countries have been emphasizing pharmacomctrics as a tool for an effective and efficient drug evaluation. Despite this international movement, the value of pharmacometrics is still poorly recognized by the Korean drug evaluation system. This study aimed to analyze the current state of utiliza-tion of pharmacometrics by foreign drug regulatory agencies and develop a road map to guide the implementation phar- macometrics into the Krean drug evaluation system. MEDLINE and foreign drug regulatory agency database were extensively searched to obtain scientific research articles, guidance, regulations and pharmacometric review reports on foreign pharmacometric drug evaluation system. A systematic roadmap comprised of 3 stages to implement pharmaco-metrics in Lorean drug evaluation system was formulated after analyzing the collected data in tune with the current evaluation system. Pharmacometrics is an urgently required tool to achieve an efficient drug evaluation and review in Korea. The road map developed by this study is expected to aid in setting up a policy to implement and utilize phar-macometrics in Korea.

Case Reports : A case of Leukemoid reaction in a patient with sarcomatous hepatocellular carcinoma

( Hyun Phil Shin ),( Jung Won Jeon ),( Jae Jun Park ),( Jae Myung Cha ),( Kwang Ro Joo ),( Joung Il Lee ),( Gou Young Kim ),( So Young Kang ) 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3

A leukemoid reaction is defined as reactive leukocytosis exceeding 50,000/mm3, with a significant increase in early neutrophil precursors, and can be a paraneoplastic manifestation of various malignant tumors. A 71-year-old male patient complained of decreased appetite, fatigue, and abdominal fullness. He had a palpable, firm liver, and laboratory investigations suggested leukemoid reaction. Liver dynamic computed tomography revealed a hypervascular mass, and an ultrasound-guided fine-needle aspiration of the mass confirmed hepatocellular carcinoma (HCC) with a sarcomatoid component. The leukocyte count of the patient had increased to 147,800/mm3, and he died 10 days after admission. This is a rare case of leukemoid reaction in a patient with sarcomatous HCC. (Korean J Hepatol 2011;17:226-228)

간내담관담석 및 간내샘편평암종과 동반된 간주위 농양 1예

조창현 ( Chang Hyun Cho ),주광로 ( Kwang Ro Joo ),차재명 ( Jae Myung Cha ),박종범 ( Jong Beom Park ),이정일 ( Joung Il Lee ),주선형 ( Sun Hyung Joo ),김교영 ( Gou Young Kim ) 대한내과학회 2008 대한내과학회지 Vol.75 No.5

본 증례는 임상적으로 매우 드문 간내담관암종의 한 변형인 샘편평암종과 동측 간내담관담석이 있는 환자에서 발생된 간주위 농양 예로 농양의 원인이 간내담관의 복강내 파열인지 아니면 간내담관암종의 자연파열의 결과인지는 분명치는 않으나 매우 드물고 흥미로운 예로 생각된다. Perihepatic abscess is a serious complication of bile duct or hollow viscus injury, with significant morbidity and mortality rates. Perihepatic abscess due to non-traumatic rupture of the biliary tree usually occurs in the presence of biliary stones. In contrast, perihepatic abscess as a result of spontaneous rupture of cholangiocarcinoma is very rare; cholangiocarcinoma generally forms a hard tumor with abundant fibrous stroma, making them difficult to rupture. Here, we describe a case of perihepatic abscess associated with intrahepatic bile duct stones and ipsilateral cholangiocarcinoma. Although it is unclear whether the etiology of perihepatic abscess was rupture of the biliary tree or cholangiocarcinoma, this association is very rare and has never before been reported in the literature. (Korean J Med 75:582-585, 2008)

The Vasodilating Mechanism of Atrial Natriuretic Peptide in 2-kidney 1 Clip Renovascular Hypertensive Rats

정진영,안영철,김헌식,고규영,안희열,김명석,Jung, Jin-Young,Ahn, Young-Chul,Kim, Hun-Sik,Koh, Gou-Young,Ahn, Hee-Yul,Kim, Myung-Suk The Korean Society of Pharmacology 1996 대한약리학잡지 Vol.32 No.1

본 연구의 목적은 2-kidney 1 clip (2K-1C) 신혈관성 고혈압흰쥐에서 심방이뇨펩이드의 혈관 이완작용의 기전을 규명하고 정상혈압흰쥐에서의 혈관이완작용과 비교하는 것이다. 2K-1C 신혈관성 고혈압흰쥐는 정상혈압흰쥐에 비하여 평균동맥압의 유의한 상승과 혈장레닌활성의 증가가 관찰되었다. 2K-1C 신혈관성 고혈압흰쥐의 대동맥에서 norepinephrine (NE)의 수축력의 감수성 및 최대 수축력이 정상혈압흰쥐의 대동맥보다 증가하였다. 심방이뇨펩타이드는 NE에 의한 수축을 농도-의존적으로 각각의 혈압군에서 억제하였다. 그러나, 2K-1C 신혈관성 고혈압흰쥐에서 심방이뇨펩타이드의 NE 억제 작용은 전체적으로 정상혈압흰쥐에서 보다 감소되었다. 그러나 최대 용량의 심방이뇨펩타이드의 NE 이완작용은 양 고혈압군에서 차이가 없었다. 2K-1C 신혈관성 고혈압흰쥐에서 NE에 의하여 $Ca^{2+}$의 유입이 유의하게 증가하였고, 심방이뇨펩타이드는 이 증가를 억제하였다. 정상혈압흰쥐에서도 심방이뇨펩타이드는 NE에 의하여 유의하게 증가된 $Ca^{2+}$의 유입을 억제하였다. 이상과 같은 결과로 볼 때 정상혈압흰쥐와 2K-1C 신혈관성 고혈압흰쥐의 심방이뇨펩타이드의 이완작용의 기전에는 $Ca^{2+}$의 유입 차단이 관여할 것으로 추측되며, 이때 심방이뇨펩타이드의 NE 수축억제에 대한 potency는 2K-1C 신혈관성 고혈압 흰쥐에서 감소하였으나 efficacy는 정상혈압흰쥐와 비교하여 변함이 없음이 관찰되었다. The objectives of this study is to find out mechanism of vasodilating effects of ANP in 2K-1C renovascular hypertensive rat aorta and to compare with those of normotensive rat aorta. In 2K-1C renovascular hypertensive rat, average arterial blood pressure and plasma renin activity were higher than in normotensive rat. In 2K-1C renovascular hypertensive rat aorta, NE sensitivity was more increased and maximal contraction of aorta by NE was higher than those of normotensive rat aorta. ANP inhibited NE-induced contraction in both 2K-1C renovascular hypertensive and normotensive rat aorta, concentration-dependently. However, ANP was less effective for relaxing NE-induced contraction in 2K-1C renovascular hypertensive rat aorta than in normotensive rat aorta. ANP inhibited $^{45}Ca^{2+}$ uptake induced by NE in both 2K-1C renovascular hypertensive and normotensive rat aorta. From these results. inhibition of $Ca^{2+}$ influx may be one of the vasodilating mechanism of ANP in 2K-1C renovascular hypertensive rat aorta. Although the potency of ANP in relaxing NE-induced contractions was attenuated, the efficacy of ANP was not changed in 2K-1C renovascular hypertensive rat aorta compared with that of ANP in normotensive rat aorta. Abbreviations: ANP, Atrial natriuretic peptide; 2K-1C, 2-kidney 1 clip; NE, norepinephrine; SHR, Spontaneously hypertensive rat; DOC, Deoxycorticosterone; EDTA, Ethylenediaminetetra-acetic acid; PSS, Physiological salt solution; TRIS, tris(hydroxymethyl) aminomethane