구강 편평상피세포암종에서 STAT3 신호전달을 억제하는 genipin의 항암 효능에 관한 연구

학위논문(석사) -- 서울대학교대학원 : 치과대학 치의과학과, 2023. 8. 조성대홍성두.Background: Genipin, which is a natural compound derived from the fruit of Gardenia jasminoides Ellis, was reported to have activity against various cancer types. In this study, I determined the underlying mechanism for genipin-induced apoptotic cell death in human oral squamous cell carcinoma (OSCC). Methods: The growth inhibitory effects of genipin in human OSCC cells was examined by the Cell Counting Kit-8, soft agar, and cell line-derived xenograft assays. The effects of genipin on apoptotic cell death were assessed by nuclear morphological changes by DAPI staining, measurement of the sub-G1 population, and annexin V-FITC/PI double staining. The underlying mechanism of genipin activity was analyzed by western blotting, subcellular fractionation of the nucleus and cytoplasm, immunocytochemistry, and quantitative real-time PCR. Results: Genipin inhibited the growth of human OSCC cells both in vitro and in vivo. Genipin also induced apoptotic cell death in human OSCC cells, which was mediated through a caspase-dependent pathway. Genipin reduced phosphorylation of signal transduction and activator of transcription 3 (STAT3) at Tyr705 as well as its nuclear localization. Furthermore, the inhibition of p-STAT3Tyr705 levels following genipin treatment was required for the reduction of survivin and myeloid cell leukemia-1 (Mcl-1) expression, which resulted in apoptotic cell death. The genipin-mediated reduction in survivin and Mcl-1 expression was caused by transcriptional and/or post-translational regulatory mechanisms, which occurred in a cell context-dependent manner. Conclusions: The results provide insight into the regulatory mechanism by which genipin induces apoptotic cell death through the abrogation of STAT3 phosphorylation within the nucleus and suggest that genipin represents a potential therapeutic option for the treatment of human OSCC.1. 목 적: 이전 연구에 따르면 제니핀 (genipin)은 구강 편평상피세포암종 (OSCC)을 포함하는 여러 유형의 암에 대해 세포 독성이 있는 것으로 알려져 있다. 하지만, 구강 편평상피세포암종 세포주에서 제니핀의 항암 효능을 설명하는 메커니즘은 현재까지 미미한 실정이다. 본 연구는 구강 편평상피세포암종 세포주에서 제니핀이 유도하는 항암 효능의 근본적인 메커니즘을 규명하는 것을 목표로 한다. 2. 재료 및 방 법: 구강 편평상피세포암종에서 제니핀의 세포증식 억제 효과는 Cell Counting Kit-8, soft agar 및 세포주 유래 이종 이식 동물모델을 통해 평가되었다. 또한, 세포사멸 (apoptotic cell death)을 유도하는 제니핀의 효능은 DAPI staining을 통한 핵의 형태학적 변화, sub-G1 분석, Annexin V/PI double staining 과 cleaved PARP 및 cleaved caspase 3 단백질의 검출을 통해 평가되었다. 제니핀에 의해 매개되는 signal transduction and activator of transcription 3 (STAT3)의 활성억제 메커니즘은 western blotting, subcellular fractionation of the nucleus and cytoplasm, immunocytochemistry 와 quantitative real-time PCR을 통해 STAT3의 타겟 유전자들의 발현을 확인하였다. 3. 결 과 및 고찰: 제니핀은 in virto 및 in vivo에서 구강 편평상피세포암종에서 세포증식 억제했다. 또한 제니핀은 cleaved PARP 과 cleaved caspase 3단백질 발현을 농도의존적으로 증가시켰으며, pan-caspase 억제제인 Z-VAD-FMK를 처리함으로써, 제니핀에 의한 세포 사멸이 caspase 3에 의존적인 경로를 통하여 유도되는 것을 확인하였다. Subcellular fractionation 과 immunocytochemistry를 통해 제니핀이 핵에 존재하는 p-STAT3(Y705)의 발현을 농도의존적으로 감소시키는 것을 확인하였다. 또한, 제니핀에 의한 p-STAT3(Y705) 발현의 억제는 세포 사멸에 연관된 단백질인 survivin 과 myeloid cell leukemia-1 (Mcl-1) 발현의 감소를 초래했다. 제니핀에 의해 매개되는 survivin 및 Mcl-1 발현의 감소는 전사 및/또는 번역 후 조절 메커니즘에 의해 발생했으며, 이는 세포 맥락에 의존적인 방식으로 발생했다. 이 연구로, 제니핀이 구강 편평상피세포암종에서 STAT3의 활성을 억제하고 타겟 유전자들의 발현을 감소시킴으로써 세포사멸을 유도할 수 있는 항암 효능을 제시하였다.Abstract in English 1 Table of Contents 4 List of Figures 5 1. Introduction 7 2. Material & Methods 10 3. Results 21 4. Discussion 44 5. Conclusions 48 6. References 49 Abstract in Korean 61석

Drosophila melanogaster에서 PTP synthase를 encoding하는 purple gene의 특성 분석

학위논문(석사)--서울大學校 大學院 :微生物學科,1995.Maste

초파리(Drosophila melanogaster) tetrahydrobiopterin 재생에 관련된 dihydropteridine reductase와 pterin-4α-carbinolamine dehydratase유전자에 관한 연구

Thesis (doctoral)--서울대학교 대학원 :생명과학부,2000.Docto

인체부위의 이동순서를 이용한 RV차량에서의 운전자 승/하차 자세 분석

MasterVehicle ingress/egress is one of important ergonomic issues in automobile industry. Many researchers and car manufacturers have continued studying with this topic. Some studies were considering with joint angle movements during ingress/egress, and other studies analyzed Electromyography(EMG) signals to examine muscle usage. Among these studies, ingress/egress motion strategy is the most basic study area. It is obvious that joint angles and muscle usages are absolutely dependent on ingress/egress posture. There were other studies dealt with ingress/egress strategies. However, these studies only provide strategies what they observed by experiments. With this strategy, it is hard to classify ingress/egress motion because ingress/egress motions are continuous action. Furthermore, if observed ingress/egress motions are quite different from those strategies, it is impossible to classify a newly observed motion. Hence, in this study, we suggest vehicle driver’s seat ingress/egress motion classification methods using body segments through video observation. Head, torso, buttock, right foot and left foot were used to express ingress/egress motion. Ingress/egress motions were expressed by arranging body segments in order of each segments pass through door plane. It includes waist and neck joint bending. To increase ingress/egress motion, it suggests ingress/egress direction of torso and hand contact position. To apply this method, we conducted the ingress/egress experiments. Forty participants were recruited and three different sized RV (recreational vehicle) were used in this experiments. Each participant was instructed with the purpose of experiment and procedure, and adjusted his/her driver’s seat location. Seat location could be moved horizontally and vertically. After adjusting the seat location, they practiced freely ingress/egress on each vehicle to adapt their motion and to find the most convenient strategy. Then, the main test was conducted, in which each participant ingressed/egressed each vehicle at least 3 times and all ingress/egress motions were recorded by a video camera. For those ingress/egress motion data, the last recorded data were used for Further analysis. Total 120 of ingress motion and 120 egress motion data were analyzed by the developed method. In the ingress motion, [RF – B – T – H – LF] strategy is most frequently used by the participants. In this strategy, people put their right foot on the floor and sit on the seat with his/her buttock. Then, torso and head follows naturally and finally put their left foot in the vehicle. In the egress motion, [LF H – T – B – RF] is most frequently observed. In this strategy, people stick out their left foot and head at the same time, and raise their body from seat. Torso and buttock are sequentially got out of the vehicle. Finally, right foot is getting out of vehicle and end the egress motion. After that, we examined the result in terms of vehicle type. The results show that the ingress/egress strategies were well classified by vehicle’s characteristics. Using this method, classification of ingress/egress motions was easy. With this method, it is easy to make the database of the ingress/egress motion strategy. From the database, it is useful to focus on the most frequently observed strategy when studying the driver’s vehicle ingress/egress motion patterns

A boundary element solution for microstrip lines

학위논문(석사) - 한국과학기술원 : 전기 및 전자공학과, 1989.2, [ [ii], 47 p. ]한국과학기술원 : 전기 및 전자공학과

Microstrip line fed rectangular microstrip patch antenna and its array

학위논문(석사) - 한국과학기술원 : 전기 및 전자공학과, 1989.2, [ [iii], 60 p. ]한국과학기술원 : 전기 및 전자공학과

Perceived discomfort of design parameters during recreational vehicle ingress/egress

2