췌장암 이종이식 모델에서 Doxorubicin을 탑재한 미세기포 집합체와 집속초음파 병행 치료의 상호증강 효과

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 이재영.The synergistic effects of a doxorubicin (Dox)-loaded microparticle-microbubble complex (DMMC) and focused ultrasound (FUS) with a short duty cycle (5%) were evaluated in a pancreatic cancer xenograft model established by inoculating immunedeficient mice with CFPAC-1 cells. The efficacy of the DMMC with FUS (study 1), the effect of conjugating the particles as opposed to mixing them (study 2), and the levels of tumor apoptosis and intracellular Dox (study 3) were evaluated. The DMMC with FUS showed the lowest tumor growth rate (30.8 mm3/week) and the highest intracellular Dox uptake (8.8%) and tumor cell apoptosis rate (58.7%) among all treatments. The DMMC presented a significantly lower growth rate than the mixture of Dox-loaded microparticles and microbubbles (44.2 mm3/week, P<0.01) when they were combined with FUS. In conclusion, DMMC with short-duty-cycle FUS has promise for tumor growth suppression, which may be attributed to high intracellular Dox uptake.목적: 췌장암 이종이식 모델에서 Doxorubicin을 탑재한 미세기포 집합체 (DMMC)와 집속초음파 평행 치료의 상호 증강 효과를 평가하고자 한다. 방법: 면역결핍 마우스에 CFPAC-1을 접종하여 췌장암 이종이식 모델을 만들었다. DMMC는 Doxorubicin을 탑재한 알부민 미세입자와 미세기포와의 결합을 통해 생성하였다. 집속초음파 치료를 위해 음향파워 80.5W, 반복 주기 (duty cycle) 5%를 적용하였다. 마우스는 총 5 군 (집단 별 개체 수=5) 으로 나누어 4mg/Kg Doxorubicin로 치료를 시행하였다. 5군은 1) 대조군, 2) Doxorubicin 단독, 3) Doxorubicin와 미세기포 혼합물에 집속초음파 치료, 4) Doxorubicin 탑재 알부민 미세입자와 미세기포 혼합물에 집속초음파 치료, 5) Doxorubicin 탑재 알부민 미세입자와 미세기포 집합체 (DMMC)에 집속초음파 치료로 이루어져 있다. 제 1단계에서는 DMMC와 집속초음파 치료의 효과를 확인하고자 하였다. 제 2단계에서는 혼합물과 집합체의 치료효과를 비교하고자 하였다. 병태생리학적 분석을 위해, 동일한 조건으로 반복 실험 하였고, 종양 apoptosis와 세포 내 Doxorubicin 흡수 양 을 형광분석을 통해 분석하였다. 통계분석에는 Bonferroni correction을 동반한 Kruskal-Wallis 검정과 Mann- Whitney 검정을 이용하였다. 결과: 제 1단계 실험에서 DMMC와 집속초음파 병행치료를 시행한 군에서 유의하게 작은 종양크기 및 가장 느린 종양 성장속도를 보여주었다. 제 2단계 실험에서는, 유일하게 DMMC와 집속초음파 병행치료를 시행한 군에서 대조군과 비교시 유의하게 낮은 성장속도를 보여주었다 (P=0.01). 병태생리학적 분석에서, DMMC와 집속초음파 병행치료를 시행한 군이 Doxorubicin 단독치료 혹은 Doxorubicin과 FUS 병행 치료군보다 높은 세포 내 Doxorubicin 흡수를 보였다 (Ps<.001). DMMC와 집속초음파 병행 치료 군에서 종양세포 apoptosis 비율이 다른 실험군과 비교시 가장 높았다. 결론: DMMC와 집속초음파 병행치료는 췌장암 세포의 종양의 성장을 억제할 수 있는 것으로 사료되며, 이는 세포내의 높은 Doxorubicin 흡수에 기인한 것으로 보인다.Chapter 1. Introduction 1 Chapter 2. Materials and Methods 4 Chapter 3. Results 14 Chapter 4. Discussion 34 Chapter 5. Conclusion 41 References 42 Abstract in Korean 51Docto

췌장 IPMN의 악성도 평가: Multidetector CT와 MR/MRCP의 비교

학위논문 (석사)-- 서울대학교 대학원 : 임상의과학과, 2015. 2. 이정민.Introduction: To compare the diagnostic performances of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) in predicting the malignant potential of pancreatic intraductal papillary neoplasms (IPMN) and to evaluate their inter-modality agreement. Material and Methods: Institutional review board approval was obtained and the requirement for informed consent was waived for this retrospective study. In 129 patients with pathologically-proven pancreas IPMNs, three reviewers independently evaluated their preoperative MDCT and MRI with MRCP findings. Inter-modality agreement between MDCT and MRI with MRCP as well as interobserver agreement of each imaging modality in detecting high-risk stigmata and worrisome features were assessed. Diagnostic values of other signs of overt malignancy including the presence of parenchymal mass and locoregional extension were analyzed. Diagnostic performances and inter-modality consistency were assessed using receiver operating curve (ROC) analysis and weighted κ statistics. Results: Overall predictability of MDCT and MRI with MRCP for the malignancy potential of pancreatic IPMNs was similar (AUC: 0.82 and 0.82, respectively) with good inter-modality agreement (κ=0.75) and moderate interobserver agreement (κ=0.47~0.59) when we set high-grade dysplasia as the cutoff for malignancy. When parenchymal masses and locoregional extensions were considered as overt malignant signs, invasive IPMN predictability was significantly increased (AUC: 0.87 for CT and 0.88 for MRI) with high sensitivity (94.3%) and equivocal specificity (69.1%). Conclusion: Diagnostic performances in predicting the malignant potential of pancreatic IPMNs using MDCT and MRI with MRCP were similar while showing good inter-modality agreement, suggesting that interchangeable follow-up may be possibleAbstract i Contents iii List of tables and figures iv Introduction 1 Material and Methods 5 Results 16 Discussion 34 Appendix 40 References 42 Abstract in Korean 50Maste

Comparing Properties of Variable Pore-Sized 3D-Printed PLA Membrane with Conventional PLA Membrane for Guided Bone/Tissue Regeneration

The aim of this study was to fabricate bioresorbable polylactide (PLA) membranes by 3D printing and compare their properties to those of the membranes fabricated by the conventional method and compare the effect of different pore sizes on the properties of the 3D-printed membranes. PLA membranes with three different pore sizes (large pore-479 μm, small pore-273 μm, and no pore) were 3D printed, and membranes fabricated using the conventional solvent casting method were used as the control group. Scanning electron microscopy (SEM) and micro-computed tomography (µ-CT) were taken to observe the morphology and obtain the porosity of the four groups. A tensile test was performed to compare the tensile strength, elastic modulus, and elongation at break of the membranes. Preosteoblast cells were cultured on the membranes for 1, 3 and 7 days, followed by a WST assay and SEM, to examine the cell proliferation on different groups. As a result, the 3D-printed membranes showed superior mechanical properties to those of the solvent cast membranes, and the 3D-printed membranes exhibited different advantageous mechanical properties depending on the different pore sizes. The various fabrication methods and pore sizes did not have significantly different effects on cell growth. It is proven that 3D printing is a promising method for the fabrication of customized barrier membranes used in GBR/GTR.ope

Therapeutic effects of a mesenchymal stem cell‑based insulin‑like growth factor‑1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model

The present study was conducted in order to improve gene expression efficiency of insulin‑like growth factor‑1 (IGF‑1)‑transfected mesenchymal stem cells (MSCs) using a non‑viral carrier and a simplified method of dual gene selection. The therapeutic efficacy of this MSC‑based IGF‑1/enhanced green fluorescent protein (EGFP) dual gene sorting system was evaluated in a rat myocardial infarction (MI) model. IGF‑1 and EGFP genes were expressed in MSCs in vitro. The purity of dual gene‑expressing MSCs was 95.1% by fluorescence‑activated cell sorting. Transfected MSCs injected into rats were identified based on green fluorescence, with an increased signal intensity observed in rats injected with sorted cells, compared with unsorted cells. IGF‑1 expression levels were additionally increased in the sorted group, and decreases in infarct size, fibrotic area and fraction of apoptotic cells were observed. These results demonstrated that IGF‑1 overexpression protects against fibrosis and apoptosis in the myocardium and reduces infarct size following MI. Additionally, the present vector sorting system may potentially be applied to other types of stem cell‑based gene therapy.ope

Effects of 1% Lidocaine Instillation on Overactive Bladder Induced by Bladder Outlet Obstruction in Rats

Purpose: Lidocaine is a common local anesthetic and antiarrhythmic drug that acts via the local anesthetic effect of blocking voltage-gated sodium channels in peripheral neurons. To evaluate lidocaine as a therapeutic agent, we investigated optimal concentrations and effects of intravesical lidocaine instillation in a bladder outlet obstruction (BOO)-induced rat model of overactive bladder (OAB). Materials and methods: To determine the therapeutic dosage of lidocaine, 16 female Sprague-Dawley (SD) rats (mean weight = 200 ± 20 g) were divided into four treatment groups: those receiving saline, 0.5% lidocaine, 1% lidocaine, and 2% lidocaine (n = 4 per group). Twenty-four additional SD rats were divided into two groups to investigate the effect of 1% lidocaine treatment in rats with BOO and normal rats (n = 12 per group). Cystometry was performed by infusing physiological saline and lidocaine into the bladder at a slow infusion rate (0.04 mL/min). Cystometric parameters were analyzed using PowerLab®. The expression of c-Fos, a protein expressed by C-fibers in the spinal cord (L6), was investigated via western blotting. Results: Among the test lidocaine doses, only 1% lidocaine increased the intercontraction interval (ICI) (control mean = 500.56 ± 24.4 s; treatment mean = 641.0 ± 49.3 s; p < .01) without changes in threshold pressure and basal pressure. In the BOO-induced OAB group, the ICI increased significantly after instillation of 1% lidocaine (control mean = 135.8 ± 12.87 s; OAB-group mean = 274.2 ± 33.21 s; p < .01). Detrusor overactivity and non-voiding contraction were observed in the control group but not in rats with BOO after lidocaine instillation. The expression of c-Fos in C-fibers in the spinal cord (L6) decreased significantly after 1% lidocaine treatment in rats with BOO. Conclusion: Intravesical instillation of 1% lidocaine improves cystometric parameters without deterioration of contractility by blocking excessive C-fiber activity in the rat model of BOO-induced OAB. Therefore, instillation of 1% lidocaine has minimal effects on normal nerves while blocking nerves that contribute to OAB. Our findings suggest that intravesical instillation of 1% lidocaine is a useful treatment for OAB.ope

Function of the Cold Receptor (TRPM8) Associated with Voiding Dysfunction in Bladder Outlet Obstruction in Rats.

PURPOSE: Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO. METHODS: Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: Cystometry showed that the intercontraction interval (ICI; 428.2±23.4 vs. 880.4±51.2, P<0.001), micturition pressure (MP; 25.7±1.01 vs. 71.80±3.01, P<0.001), and threshold pressure (2.9±0.25 vs. 9.2±1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group. CONCLUSIONS: Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca(2+) from the extracellular space or stores. The increase of Ca(2+) probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.ope

T 임파구에서 레티노이드와 그 수용체가 Nur77의 전사 기능에 미치는 영향

Dept. of Medical Sciences/석사ope

RESD : a regulatory element SNPs database in human

Thesis(master`s)--서울대학교 대학원 :협동과정 생물정보학전공,2004.Maste

이강덕 가야금 협주곡 연구 : <가야금 협주곡> 제 2번을 중심으로

학위논문(석사)--서울대학교 대학원 :음악학과 국악기악전공,2001.Maste