• 대한한의학방제학회지
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• 제23권2호
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• pp.199-208
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• 2015

Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

• 대한영상의학회지
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• 제82권4호
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• pp.994-999
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• 2021

수술 이후 10년 이상이 경과된 후 발생하는 후발성 전이와 더불어 기관지 내 전이는 신세포암의 특징적인 소견이다. 본 증례 보고는 신절제술 20년 후에 세분절 기관지에서 발생한 신세포암의 단일성 기관지 내 전이의 사례를 보고하고 문헌을 고찰하고자 한다. 71세의 남자가 폐렴을 주소로 병원에 입원하였다. 흉부 단순촬영에서 우하폐야의 다발성 결절성 병변을 보여 흉부 컴퓨터단층사진을 촬영하였고 우폐의 염증성 침윤과 함께 우하엽에 4.3 cm 크기의 경계가 좋은 길쭉한 고형성 종괴를 발견하였다. 포함된 상복부에 우측 신절제술의 흔적으로 20년 전에 투명 신세포암으로 우측 신장 절제술을 받았던 기왕력을 확인하였다. 병변은 폐우하엽 절제술로 제거하였고, 병리학적으로 기관지 내 전이성 투명신세포암으로 진단되었다. 신세포암의 병력이 있다면 절제술 후 수십 년이 지난 후라도 기관지 내 종양에 대하여 신세포암의 기관지 내 전이 가능성을 고려하여야 한다.

• Korean Journal of Radiology
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• 제21권6호
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• pp.670-683
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• 2020

Objective: The presence of coagulative necrosis (CN) in clear cell renal cell carcinoma (ccRCC) indicates a poor prognosis, while the absence of CN indicates a good prognosis. The purpose of this study was to build and validate a radiomics signature based on preoperative CT imaging data to estimate CN status in ccRCC. Materials and Methods: Altogether, 105 patients with pathologically confirmed ccRCC were retrospectively enrolled in this study and then divided into training (n = 72) and validation (n = 33) sets. Thereafter, 385 radiomics features were extracted from the three-dimensional volumes of interest of each tumor, and 10 traditional features were assessed by two experienced radiologists using triple-phase CT-enhanced images. A multivariate logistic regression algorithm was used to build the radiomics score and traditional predictors in the training set, and their performance was assessed and then tested in the validation set. The radiomics signature to distinguish CN status was then developed by incorporating the radiomics score and the selected traditional predictors. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance. Results: The area under the ROC curve (AUC) of the radiomics score, which consisted of 7 radiomics features, was 0.855 in the training set and 0.885 in the validation set. The AUC of the traditional predictor, which consisted of 2 traditional features, was 0.843 in the training set and 0.858 in the validation set. The radiomics signature showed the best performance with an AUC of 0.942 in the training set, which was then confirmed with an AUC of 0.969 in the validation set. Conclusion: The CT-based radiomics signature that incorporated radiomics and traditional features has the potential to be used as a non-invasive tool for preoperative prediction of CN in ccRCC.

• 대한영상의학회지
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• 제84권2호
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• pp.409-417
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• 2023

목적 근치적 방광적출 후 회장 신방광형성술을 시행 받은 방광암 환자는 수술 후 혈뇨를 보일 수 있는데, 이는 종양 재발에 대한 불안을 유발할 수 있다. 그러나 종양 재발뿐 아니라 호두까기 증후군이 수술 후 혈뇨의 원인이 될 수 있으며, 이는 빈번한 증후군일 수 있음을 증명하려고 한다. 대상과 방법 2011년부터 2016년까지 근치적방광적출 후 회장 신방광형성술을 시행 받은 255명의 방광암 환자를 대상으로 조영증강 복부골반 컴퓨터단층촬영과 소변검사 소견을 후향적으로 분석하였다. 컴퓨터단층촬영에서 호두까기 증후군 소견의 유무는 좌신정맥 흐름 패턴을 평가하여 판단하였다. 소변분석에서는 총 소변검사에서 혈뇨가 양성인 비율에 따라 환자를 분류하였다. 결과 컴퓨터단층촬영에서 호두까기 증후군 소견은 135명의 환자 중 31.9%에서 나타났다. 혈뇨 양성 그룹에서는 호두까기 증후군의 소견이 없는 환자보다 있는 환자가 26% 더 많았다. 결론 호두까기 증후군의 소견은 수술 후 방광암 환자에게 빈번하였으며, 호두까기 증후군 소견과 혈뇨 사이에는 유의미한 상관관계가 있었다. 또한 호두까기 증후군 소견의 유병률은 수술 후 요로의 종양 재발률보다 높았다.

• Oncology Letters
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• 제42권1호
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• pp.453-460
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• 2019

The present study aimed to identify novel methylation markers of clear cell renal cell carcinoma (ccRCC) using microarray methylation analysis and evaluate their prognostic relevance in patient samples. To identify cancer-specific methylated biomarkers, microarray profiling of ccRCC samples from our institute (n=12) and The Cancer Genome Atlas (TCGA) database (n=160) were utilized, and the prognostic relevance of candidate genes were investigated in another TCGA dataset (n=153). For validation, pyrosequencing analyses with ccRCC samples from our institute (n=164) and another (n=117) were performed and the potential clinical application of selected biomarkers was examined. We identified 22 CpG island loci that were commonly hypermethylated in ccRCC. Kaplan-Meier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, Kaplan-Meier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G protein-coupled receptor 149 (GPR149), was significantly associated with shorter time-to-progression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression. Similarly, the methylation status of these two genes was significantly associated with poor outcomes in the independent external validation cohort. Collectively, the present study proposed that the novel methylation markers ZNF492 and GPR149 could be independent prognostic indicators in patients with ccRCC.

• 약학회지
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• 제48권6호
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• 대한골관절종양학회지
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• 제7권4호
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• pp.133-138
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• 2001

목적 : 전이성 골종양의 임상적인 양상과 골전이 후의 생존률을 분석하고자 하였다. 대상 및 방법 : 1982년 1월부터 1998년 12월까지 전이성 골종양으로 진단된 198례를 대상으로 성별 및 연령별 분포, 골 전이 장소, 골 전이가 되기까지의 기간, 골 전이 후 생존률을 조사하여 통계학적 분석을 하였다. 결과 : 198례 중 평균 연령은 57세(24~86세)였고, 198례 중 폐암 64례(32.3%), 유방암 32례(16.2%)가 가장 흔한 원발성 암이었으며, 척추가 가장 흔한 전이장소였으며 특히 요추가 49례(37.8%)로 가장 많았다. 198례 중 추시가 가능했던 115례에서 생존분석을 하였는데 평균 생존기간은 15.3개월이었으며 폐암(8.72개월), 간암(7.09개월), 신장암(4.8개월)에서 짧았고, 유방암(54.14개월)에서 길었다. 결론 : 전이성 골종양의 평균 연령은 과거에 보고된 수치에 비해 증가하였고, 중심골격 특히 척추로의 전이가 타 부위에 비해 월등히 높았으며, 1년 생존률 30.43%, 5년 생존률 6.08%로 시간의 경과함에 따라서 사망률이 급격히 증가하므로 조기 진단이 골전이 후의 생존율에 영향을 미치는 중요한 인자라고 사료된다.

• 대한골관절종양학회지
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• 제20권2호
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• pp.47-53
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• 2014

목적: 저등급 중심부 골육종 환자의 진단, 치료 및 예후에 대하여 알아보고자 하였다. 대상 및 방법: 1994년부터 2011년까지 저등급 중심부 골육종으로 진단받고 본원에서 치료받은 16명의 환자를 대상으로 하였다. 결과: 환자 분포는 남자가 4명 여자가 12명이었으며 평균 연령은 26세였다. 초기 진단은 11명의 환자가 중심부 저등급 골육종으로 맞게 진단되었으나 나머지 5명의 환자는 각각 유골 골종, 비골화성 섬유종, 골모세포종, 동맥류성 골낭종, 결합조직형성 섬유종 등으로 오진되었다. 15명의 환자가 최종적으로 광범위 절제술을 시행하였으며 그 중 한 명은 수술 전 항암치료를 시행하였다. 그 중 14명의 환자가 치료 후 재발 없이 추시중이며, 한 명은 기존에 앓던 신세포암의 악화로 수술 후 21개월 후 사망하였다. 나머지 한 명은 다발성 종양 환자로, 부분적으로만 광범위 절제술을 시행하였으며 잔존 종양에 방사선 치료만을 시행한 후 7년째 생존 중이다. 9명(56%)의 환자가 종양이 피질골 밖까지 파급되어 있는 소견을 보였으며 그 중 한 명은 구획 외로까지의 파급을 보였다. 결론: 저등급 중심부 골육종은 진단이 어려우나 임상적 의심과 함께 조직병리학적, 영상학적인 특징을 고려하여 주의 깊은 감별이 요구된다. 치료에 있어서는 광범위 종양 절제술이 권장되며, 양성 종양으로 오진하여 병소내 절제술만 시행한 경우라도 국소 재발이나 고등급으로의 악성 전환 가능성이 있으므로 광범위 재절제술을 시행할 것을 권고하는 바이다.

• Journal of Gastric Cancer
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• 제21권2호
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• pp.191-202
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• 2021

Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (K_D=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (K_D=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions: Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.

• 대한수의학회지
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• 제54권4호
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• pp.225-231
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• 2014

Klotho deficiency is an early event in acute kidney injury (AKI) that exacerbates acute kidney damage. The present study explored the expression of Klotho and inflammation related factors in cisplatin-induced AKI. Rats (n = 18) were treated with cisplatin intraperitoneal injection (5 mg/kg) or left untreated as controls (n = 6), then sacrificed at 5 (n = 6) and 10 days (n = 6) treatment. Five days after cisplatin injection, the serum kidney enzymes and kidney cell apoptosis were significantly increased. Moreover, the expression of Klotho was decreased when compared to the control group, especially in the cortex and outer medulla regions. In contrast, inflammation related signals including nuclear factor kappa B, tumor necrosis factor-${\alpha}$, and tumor necrosis factor-like weak inducer of apoptosis were enhanced. However, 10 days after cisplatin injection, Klotho expression was enhanced upon both IHC and Western blot analysis, with slightly recovered renal function and decreased apoptosis. Furthermore, inflammation related signals expression was decreased relative to the 5 days group. Overall, this study confirmed the opposite expression patterns between Klotho and inflammation related signals and their localization in cisplatin-induced AKI kidney.