Interval Change of Breast Lesions Initially Categorized as Probably Benign on Breast US : Are There Any Differences Between Benign and Malignant Lesions?

장자윤 忠南大學校 大學院 2016 국내석사

목적 본 연구는 유방 초음파에서 category 3 – probably benign finding으로 분류된 lesion이 추적 초음파에서 interval change를 보인 경우 malignancy rate 및 benign과 malignancy 사이에 imaging finding의 차이가 있는지를 비교하고자 하였다. 대상 및 방법 본 연구는 2004년 6월부터 2014년 12월까지 시행된 초음파 유도 총생검 11,323건 중 2년 이내 초음파 결과가 category 3 - probably benign finding이었으나 interval change를 보였던 288개의 병변을 대상으로 후향적으로 분석하였다. 최종 병리 결과에 따라 malignancy와 benign lesion 두 group으로 분류하여 maximal diameter change, maximal diameter change per month, maximal diameter change per initial diameter, 그리고 maximal diameter change per initial diameter per month를 비교하였다. 모양 변화가 있었던 병변과 없었던 병변 사이의 malignancy rate도 비교하였다. 결과 Interval change를 보인 병변의 malignancy rate은 6.6%였으며, malignancy 군에서 maximal diameter change (4.0mm), maximal diameter change per month (0.6mm), maximal diameter change per initial diameter (88.6%), 그리고 maximal diameter change per initial diameter per month (9.3%)로 모두 benign군과 비교하여 의미 있게 큰 크기 변화를 보였다 (p=0.002, 0.013, <0.001, <0.001). Malignancy를 예측하는 지표로 가장 정확도가 높은 것은 maximal diameter change per initial diameter 였으며, cut-off value는 39.0% 였다 (sensitivity 94.7%, specificity 53.5%). Morphologic change가 있는 군에서 malignancy rate (9.2%)이 좀 더 높았지만, morphologic change가 없는 군 (5.5%)과 비교시 통계적으로 유의한 차이는 보이지 않았다. 결론 유방 초음파에서 category 3 – probably benign finding으로 분류된 병변이 initial diameter와 비교시 39.0% 이상 크기 변화를 보일 때 malignancy를 가능성이 6.6% (sensitivity 94.7%, specificity 53.5%)로 조직검사를 통한 확인이 반드시 필요하다. 또한 probably benign finding이 추적 관찰에서 interval change를 보인 경우 malignancy를 예측하는 데에는 병변의 크기 변화가 morphologic change보다 더 도움이 될 수 있다.

Optogenetic stimulation promotes axon outgrowth of motor neuron in vitro

장자윤 이화여자대학교 대학원 2016 국내석사

Axons of motor neurons play crucial role in conveying electrical signals from the spinal cord to muscles, gland and other effector organs. Motor neuron disease (MND) or spinal cord injury (SCI) has common symptom which is degeneration of motor neurons’ axons. Degeneration of axons may induce the disorder of motor function because of the failure of the movement commands from spinal cord. Therefore, axon regeneration is critical in recovering lost functions in this situation. To promote the axon regeneration, numerous strategies have been investigated including the application of neurotrophic factors or electrical stimulation. Here we suggest a new method to promote axon outgrowth. Since optogenetic can regulate membrane potential through specific wavelength light was applied to motor neurons (MNs), we examined the effectiveness of Channelrhodopsin (ChR) on the axon generation. MNs were transfected with CatCh, a calcium translocating ChR. The transfected MNs were stimulated by a custom-built array of 473nm light-emitting diode (LED) which is close to the excitation peak wavelength of CatCh. On the following day, the MNs were fixed and analyzed. The length of axon growth was quantified using beta-III tubulin immunocytochemistry. The axon length of transfected MNs was about 2.4 times longer than that of control MNs. We also quantitatively examined the effect of ChR stimulation on the expression of intracellular second messenger Adenosine-3’, 5’-cyclic monophosphate (cAMP) which is well known for promoting neurite outgrowth. The concentration of cAMP was higher in the CatCh-transfected and optically stimulated MNs than the one of control condition without optogenetic stimulation. These results suggest that the optogenetic modulation of motor neurons can be effective in axon sprouting acceleration. 운동성 뉴런의 축삭 돌기는 전기적인 신호를 척수로부터 근육, 샘, 그리고 다른 장기들에 전달하는 중요한 역할을 한다. 목표 장기에 전달된 신호는 근육을 움직이거나 호흡을 하는 등의 역할을 하게 된다. 운동성 뉴런의 축삭 돌기가 손상을 입게 되면 전기적인 신호가 근육 또는 장기에 도달하지 못하게 되어 운동성 기능 장애를 유발한다. 운동 뉴런 질환 (Motor neuron disorder, MND) 또는 척수 손상 (Spinal cord injury, SCI)에 의해 축삭 돌기의 손상이 유발된다. 이 때 손상 된 축삭 돌기의 재생성은 운동성 기능 회복에 중요한 역할을 한다. 현재 손상된 축삭 돌기의 재생성을 촉진 시키기 위한 방법으로 neurotrophic factor 첨가 또는 전기자극 등의 방법이 연구되어 오고 있다. Nerve growth factor (NGF) 또는 Brain-drived neurotrophic factor (BDNF) 등을 사용하여 축삭 돌기 생성에 미치는 영향을 알아보는 실험이 연구되어 왔으며, 전기자극이 축삭 돌기의 생성에 미치는 영향을 알아보는 연구가 진행되고 있다. 본 논문에서는 축삭 돌기의 재생산을 위한 방법으로 광유전자 기법을 적용하였다. 광유전자 기법이란, 특장 파장대의 빛에 의해 세포막 전위를 조절할 수 있는 방법으로 광유전자를 운동성 뉴런에 적용하고 광유전자가 축삭 돌기의 생산에 미치는 효과를 알아보았다. 광유전자 종류의 하나로써 CatCh (Calcium translocating channelrhodopsin) 유전자를 사용하였으며 이는 자체 제작 한 473 nm 파장의 LED 자극 시스템에 반응하였다. CatCh 유전자가 발현된 운동성 뉴런에 LED 자극을 주고 그 다음날 세포를 고정시켜 면역 세포 화학적 분석방법을 사용하여 축삭 돌기의 길이를 분석하였다. 동일한 기간으로 세포 배양을 시행 했을 때, LED 자극을 한 세포의 축삭 돌기의 길이는 LED 자극을 하지 않은 세포에 비하여 약 2.4배 더 길게 자란 것을 확인 하였다. 또, 축삭 돌기의 성장에 관련된 단백질 Adenosine-3’, 5’-cyclic monophos-phate (cAMP) 분석을 하여 LED 자극이 가해진 세포에서 cAMP의 농도가 높아졌음을 확인함으로써 면역화학적 분석법에 의한 결과를 뒷받침할 수 있는 결과를 얻었다. 본 연구에서는 광유전자가 운동성 신경세포의 축삭 돌기의 성장에 도움을 주는 것을 보았다. 이 연구를 통해 광유전자 기법이 축삭 돌기의 재생성에 효과적인 방법으로써 사용될 수 있을 것으로 기대한다.

Potential roles of Brp-39 in inflammation-associated murine preterm birth

장자윤 성균관대학교 일반대학원 2013 국내석사

조산은 다양한 원인에 의해 일어나는 일종의 증후군으로서 다양한 발생 원인에 공통적으로 작용하는 기전이 모체-태아간의 염증 반응이다. CHI3L1 단백이 Th2 염증반응에 주요 역할을 한다는 점을 미루어 보아 조산과 CHI3L1 단백 간의 연관성을 조사하고자 하였다. CHI3L1 단백질의 생쥐의 상동 단백질인 Brp-39 돌연변이 생쥐와 정상 생쥐에서 염증으로 인한 조산을 유도하여 염증 반응을 비교 관찰하였다. 임신한 각각의 생쥐에 LPS 또는 PBS를 주사한 후 6시간 또는 24시간에 해부하여 얻어진 자궁과 태반 조직으로 실시간 중합효소 연쇄반응과 염색을 시행하였다. LPS 주사 후 염증으로 유도한 조산 시작시간을 비교해보면 Brp-39 돌연변이 생쥐 (20시간)가 정상 생쥐 (18시간)에 비해 조산까지의 시간이 지연된 것을 확인하였고 정상 생쥐는 대부분 (92%)의 태아를 출산한 반면 돌연변이 생쥐는 더 적은 수 (58%)의 태아를 출산하였다. 사이토카인 mRNA 발현정도와 침윤한 면역세포 양상은 Brp-39 돌연변이 생쥐와 정상 생쥐 간에 유의한 차이가 없었다. 실험 결과를 통해 Brp-39가 염증으로 인한 조산에 있어서 역할을 하고 있다는 것을 알았지만 어떤 기전에 의해 결과가 나타나는 지는 구체적으로 알 수 없었다. 따라서 추후의 연구를 통해 Brp-39이 조산에 어떤 기전을 통해 관여하는 지 밝히고자 한다. Backgrounds: Breast regression protein 39 (Brp-39) is a mouse homolog of human CHI3L1 which belongs to chitinase family that break down glycosidic bonds in chitin. Brp-39 binds to chitin but do not have enzymatic function, therefore it is called as a chitinase like molecule and it has been reported to play a role in inflammatory reaction and tissue remodeling. A recent study demonstrates that Brp-39 plays an essential role in Th2 and IL-13-induced responses. Inflammatory response is essential for physiologic parturition as well as preterm labor/birth. This study was conducted to determine the significance of Brp-39 in a murine preterm birth model. Methods: Pregnant Brp-39 (-/-) (n=18) or Brp-39 (+/+) (n=23) mice at ED 15 were injected intraperitoneally with LPS (1.5mg/kg) or PBS. Pregnancy outcomes by dissection after 6 hr and 24 hr, cytokines expression by performing qRT-PCR and inflammatory cell infiltration in maternal and fetal tissues by H&E stain and immunohistochemical stain were evaluated. Results: LPS induced preterm birth in both Brp-39 (-/-) and Brp-39 (+/+) mice, but Brp-39 (-/-) mice gave birth later than Brp-39 (+/+) mice (20 hr vs. 18 hr). Only 8% of embryos of Brp-39 (+/+) dams remained in the uterus, whereas 42% of embryos of Brp-39 (-/-) were detected in the uterus. mRNA expressions of IL-1β, IL-6, IL-10, TNF and MIP-2 in uteri and placentas were not significantly different between Brp-39 (+/+) and Brp-39 (-/-) mice. The uterine tissues of both Brp-39 (+/+) and Brp-39 (-/-) mice showed similar inflammatory cell infiltration. Neutrophils were increased in LPS groups than in PBS groups, but macrophages and NK cells were not different among all groups. Conclusions: Delayed and incomplete preterm birth in Brp-39 (-/-) mice suggests a role of Brp-39 in endotoxin-induced preterm birth. However, cytokine expression and inflammatory cell infiltration associated with preterm birth were not significantly affected by Brp-39 expression. Therefore, further study for figuring out mechanisms how Brp-39 affects preterm labor in inflammation-associated pregnancy is needed.

Functional Implications of Leucyl-tRNA synthetase in colorectal cancer

장자윤 서울대학교 융합과학기술대학원 2016 국내석사

Colorectal cancer is one of challenging cancers that has high incidence rate and death rate at the same time [1]. However, since the effective targets and chemotherapeutic agents used in clinic are lack, it is necessary to identify the new drug target for controlling colorectal cancer. Here we found that leucyl-tRNA synthetase (LRS), known as a leucine sensor of mTOR signaling, is highly expressed in colorectal cancer patient tissues as well as diverse colorectal cancer cell lines [2, 3]. LRS expression significantly promotes cancer cell growth and proliferation as determined by immunoblotting, immunohistochemistry, [35S] Met incorporation, anchorage independent growth, and xenograft assay. In addition, LRS expression is positively correlated with phosphorylation of S6Kinase which is a downstream effector of mTOR. Silencing of LRS attenuates the phosphorylation of S6K, oncogenic growth, tumor mass while increase of LRS expression enhances tumorigenic propensity. Therefore, the regulation of mTOR-S6kinase pathway via suppression of LRS expression is effective way to control cancer cell growth. Taken together, this is consistent with observation that LRS may be suggested as a potential therapeutic target to control colorectal cancer and that effective tools for LRS are needed further validation and study.

兒童用 漢字敎材 硏究

장 자윤 慶北大學校 2005 국내석사

The present teaching of Chinese in Korea has two systems. One is official system and the other is private teaching. The official system has its vulnerable point on this matter because Chinese is designated as a selective subject by the Education Department, while private teaching is enjoying the high fever of Chinese learning against all odds. This system has molded a new market that now has a scale of hundreds of billion Won. The publications related to teaching Chinese has been increasing since the mid 1990s. The contemporary understanding of Chinese has changed the object of the learning of this letter, and we can notice this through the books published. This large market reflects the necessity of Chinese in Korea. This can't be overlooked because elementary school children have no secure official system on this matter. But till now, the study of Chinese has been tilted by Korean official system and this set up its limited boundary only to the textbooks for middle and high school students. In this thesis all these publications classified into each distinct types. This classification shows the publications in the private teaching market have its own role that reflects the contemporary need of teaching Chinese. The various approach of these publications has its own value of method in education. While the books from the official Chinese education system push children to cram Chinese charaters into their head and minimize the primitive learning points in studying Chinese, the private teaching system has published books that have resourceful explanation and deep understanding. These books have suggested a various types including comic book and fairy book style. Especially the comic book style has given tangibility on Chinese alphbet to student through picture access. Fairy book style has grafted literature onto the learning system and opened a new possibility through caching the organic construction of the letter. The market dominating books are majorly mixed and fairy book style. These books represent the new trend of being functional and accessible in learning Chinese. But this trend shows its limits because the market has finally saturated and it has craved commercial applications. Here are the suggestions for this problem. Firstly, setting up the systemical place of Chinese learning and the basic condition of it is needed. In the private learning the degree of achievement is on the system and contents of the books because there is no course for teachers. The type, sound, meaning of the letter, the number of touching for making a letter, and the principle of a letter should be applied on each learning step. The coordination between these two systems should be considered too. In fact, there is no possiblity of avoiding the overlapping parts between this two systems. In this circumstance, the functional points of reading and writing alphabet and the understanding of the charater of the letter should go together. Through this these two market can help with each other. Secondly, avoiding too much commercialism is needed. The untimate goal of learning Chinese is the harmonious using of language, but in Korea the formal things, for example, qualifications through tests are the main purpose to learning Chinese. The private publication market evoked this undesirable problems and it formed a vicious circle. Especially the teaching materials for children are more expendable than those for adults, and it is difficult to have have serious feedback on these materials. This has made the mixed type and comic book type books evolved until they are the major types in the market. But now is the time to lead the quantity base to quality base after all these things. At least, it is sure that the books for children suggested the basic elements of studying and made an attempt of the change in understanding Chinese. Thirdly, the teaching materials should come up to the contemporary needs which are very weak now due to their dependence on education media and methodology. Because the main controversal point of using Chinese is on the proportion of it in Korean, there is a need to reflect the contemporary circumstance. Lastly, securing professionals in teaching Chinese is critical. All the suggestions mentioned above can be materialzed only if there are professionals and precise plans by them. Exactness in knowlege diffusion should be the essential element in writing books. However the private companies lack the efforts of employing professional Chinese learning planners for them. Without professional knowlege about literature and documents, a writer is supposed to rely on convenience and write books to cater the students. This is to distort the nature of Chinese and to promote fragmentary knowlege. The matter of accessibility and convenience should subject to the exactness of books and the methodology should turn its way to the level study according to the level of understanding