• Genomics & Informatics
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• 제18권4호
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• pp.37.1-37.11
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• 2020

BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

• 대한소화기학회지
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• 제72권6호
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• pp.318-321
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• 2018

Primary neuroendocrine tumors originating from the extrahepatic bile duct are rare. Among these tumors, large cell neuroendocrine carcinomas (NECs) are extremely rare. A 59-year-old man was admitted to Sanggye Paik Hospital with jaundice that started 10 days previously. He had a history of laparoscopic cholecystectomy, which he had undergone 12 years previously due to chronic calculous cholecystitis. Laboratory data showed abnormally elevated levels of total bilirubin 15.3 mg/dL (normal 0.2-1.2 mg/dL), AST 200 IU (normal 0-40 IU), ALT 390 IU (normal 0-40 IU), and gamma-glutamyl transferase 1,288 U/L (normal 0-60 U/L). Serum CEA was normal, but CA 19-9 was elevated 5,863 U/mL (normal 0-37 U/mL). Abdominal CT revealed a 4.5 cm sized mass involving the common bile duct and liver hilum and dilatation of both intrahepatic ducts. Percutaneous transhepatic drainage in the left hepatic duct was performed for preoperative biliary drainage. The patient underwent radical common bile duct and Roux-en-Y hepaticojejunostomy for histopathological diagnosis and surgical excision. On histopathological examination, the tumor exhibited large cell NEC (mitotic index >20/10 high-power field, Ki-67 index >20%, CD56 [+], synaptophysin [+], chromogranin [+]). Adjuvant concurrent chemotherapy and radiotherapy were started because the tumor had invaded the proximal resection margin. No recurrence was detected at 10 months by follow-up CT.

• 한국식품과학회지
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• 제27권6호
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• pp.1003-1007
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• 1995

포유동물 세포인 CHL세포를 대상으로 MMC를 농도별로 투여하여 세포분열지수 및 염색체 이상 유발 및 그 양반응관계를 관찰하고 현미 추출물이 MMC에 의한 염색체 이상 빈도에 미치는 영향을 살펴보았다. 1. 대조군인 DMSO처리구에 비해 MMC 및 현미 추출물 투여에 의해 CHL세포의 세포분열 지수는 차이가 나타나지 않았다. 2. CHL 세포를 대상으로 MMC의 농도를 $0.2{\sim}5.0\;{\mu}g/assay(0.04{\sim}1.0\;{\mu}g/ml)$로 하여 염색체 이상 빈도를 살펴본 결과 $0.2\;{\mu}g/assay$에서 $3.0\;{\mu}g/assay$까지 MMC의 농가 증가함에 따라 염색체 이상의 빈도가 점차 증가하는 경향을 나타내었으며, MMC의 농도가 $3.0\;{\mu}g/assay$ 보다 높았을 경우에는 MMC에 의한 세포독성으로 염색체 이상 분석을 할 수 없었다. MMC에 의한 염색체 이상은 염색분체형의 갭과 절단이 많이 관찰되었다. 3. 세포를 변이원 MMC $2\;{\mu}g/assay(0.04\;{\mu}g/ml)$와 현미 추출물을 $0.75{\sim}10.0\;mg/assay$의 농도로 투여하였을 경우 각 농도에서 유의적으로 MMC에 의한 염색체 이상 빈도를 감소시키는 것으로 나타났으며(p<0.01, p<0.05), 현미 추출물의 농도 증가에 따라서는 염색체 이상을 나타내는 세포수가 다소 불규칙하였으나 $7{\sim}30%$로 감소하는 경향이었다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4807-4814
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• 2012

Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

• Journal of Radiation Protection and Research
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• 제20권3호
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• pp.163-168
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• 1995

비전리 방사선의 인체에 대한 작용은 최근 우리 주위에서 많이 사용되는 microwave, radio wave, laser, ultrasoundwave, ultravioletradiation 등의 문제가 될 수 있으며 본고에서는 주로 Radio Frequency Electromagnetic (RFEM) spectrum의 shortwave와 microwave의 생물학적인 작용을 정리 발표하고자 한다. RFEM에 의한 carcinogenesis에 관해서는 아직 RFEM이 인체에서는 발암물질로서 작용한다는 보고는 없으나, cancer promotion에는 작용할 것이라는 보고는 있다. chromosomal effect에 관해서는 체외실험에서 microwave에 의한 chromosome의 stickiness의 증가와 mitotic index의 변화에 관한 보고가 있다. 인체에서는 RFEM에 많이 피폭되었다고 알려진 Moscow의 미 대사관 직원 5000명을 대상으로 한 역학조사에서는 특별한 염색채 이상은 발견되지 않았다. 동구에서의 보고에 의하면 RFEM에 의한 선천성 기형아의 출산이 보고된바 있으나 출산시의 통증을 줄이기 위한 2450 MHz의 microwave를 조사한 산모 2000명 출산아에서 기형은 없었다고 한다. 인간의 행동과 정서적인 측면에서 RFEM에 의한 변화는 1974년 Sadcikoda에 의해 기술된바 있는 µwave sickness&는 irritability, 두통, 전신쇄약, 불면증, 성욕 감퇴 및 발기부전 등을 호소하는 증후군으로 주로 동유럽의 저자들에 의하여 보고되고 있으며 구 소련에서는 microwave sickness 또는 radio wave sickness는 확실한 하나의 임상병명으로 간주되고 있다. cataractogenesis에 관해서는 실험 동물에서 잘 연구되고 있으며, 사람에서도 1952년 레이다 작업종사자 에서 보고된 이후 50여례 이상의 보고가 있으나 백내장 자체가 그 발생 빈도가 높은 질환이고 많은 원인이 있으므로 아직 인간에서의 확실한 cataractogenesis에 관해서는 더욱 연구가 필요한 분야이다. radar wave에 노출된 적이 있는 군인을 대상으로 한 미 해군의 역학조사에 의하여 radar wave에 의한 uveitis, retinitis와 비진행성 백내장등이 보고되고 있으나 딴 연구에서는 입증된바 없다.

• 대한한방내과학회지
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• 제19권1호
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• pp.22-38
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• 1998

This study was to investigate the hepatoprotective and anticirrhotic effects of Ganyeumilhobang(GIE) on the acute and chronic liver injury induced by various agents. Chronic liver injury induced by dimethylnitrosamine(DMN) ; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. Acute liver njury induced by carbon tetrachloride$(CCl_4)$ and D-galactosamine ; a experimental model for acute liver injury, the administration of $CCl_4$ and the intraperitoneal injection of D-galactosamine in the rat. The development of fibrosis and acute liver injury by the three prescriptions were examined by the chemical analysis of AST, ALT, prothrombin time and hydroxyproline. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by DMN in mice was decreased by the oral administration of GIB. 2. The degree of histological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ decreased by the oral administration of GIB. 3. The increase of senun AST and ALT of mice with acute liver damage induced by $CCl_4$ and D-galactosamine was inhibited by the administration of GIB. 4. The prolongation of prothrombin time(seconds) of mice acute liver damage induced by $CCl_4$ was shortened by the oral administration of GIB. 5. The liver of mice was hepatectomized partial1y after the oral administration of GIB. The mitotic index(% of nuclei), weight of liver, contents of protein, RNA and DNA synthesis of the liver tissue were increased by the oral administration of GIB.

• 대한세포병리학회지
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• 제13권1호
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• pp.21-27
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• 2002

Papillary immature metaplasia (PIM) of the uterine cervix (Immature condyloma) is a subset of low grade squamous intraepithelial lesion (LSIL) which is frequently associated with human papilloma virus (HPV) types 6 and 11. The histologic features of PIM include filiform papillae lined by evenly spaced immature metaplastic-type cells with frequent nucleoli, mild anisokaryosis, and a low mitotic index. To characterize the cytologic changes associated with PIM, we analyzed 14 cases of PIM from our file. We reviewed biopsy slides and the cervicovaginal smears taken proximate to the time of blopsy. Histologically, nine cases had either flat condyloma (7 cases) or high grade squamous intraepithelial lesion (HSIL) (2 cases). Cytologic changes included cells in various stages of maturation with karyomegaly (14 cases), cells with irregularities in the nuclear membrane (13 cases), intermediate cells with karyomegaly(13 cases), cells with binucleatlon (13 cases), and aborted koliocytes (11 cases) Cervicovaginal smears from all cases were interpreted as atypical squamous cells of undetermined significance (ASCUS), NOS or ASCUS, rule out squamous intraepithelial lesion (SIL) or LSIL in two cases with flat condyloma or HSIL in a case with severe dysplasia. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings, but cytologic findings may resemble variable reactive conditions and immature HSIL. Therefore, it is difficult to diagnose PIM by cytology alone. However, the meticulous efforts for making the cytologic diagnoses which can Induce active management of patients are recommended because PIM is a variant of LSIL and frequently has a flat condyloma or HSIL.

• 대한수의학회지
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• 제45권3호
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• pp.391-398
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• 2005

Several studies have been performed on the bovine leukemia since bovine leukemia virus (BLV) had been detected in 1982 in Korea. We have conducted histopathological study on the bovine lymphoma caused by BLV because only limited results were reported on the pathological characterization of lymphoma. Lymphoma tissues were obtained from cattle necropsied and slaughtered during a designated period. Lymphoma was classified histopathologically according to the National Cancer Institute Working Formulation. Leukotic tissues consisted of fairly uniform sheets of closely packed medium to large lymphocytes without any architectural arrangement in all 30 cases. Twenty five cases belong to diffuse large cell type, while three cases were diffuse mixed cell type, and two cases were immunoblastic large cell type among 30 cases. Follicular type lymphoma was not detected in this study. The mitotic index of tumor cells showed average 2.5 in the field of 400X. Nuclear cleavage was detected in 53% of cases. Multi-nucleated cells were detected among tumor cells in 30% of lymphoma cases. In conclusion, the most common morphologic cell type of bovine lymphoma in Korea was a diffuse large cell type with multinucleated cells and nuclear cleavages.

• 정보처리학회논문지:소프트웨어 및 데이터공학
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• 제5권6호
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• pp.267-272
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• 2016

생물정보학분야에서 현미경을 통해 얻은 세포 영상은 생물학적 정보를 얻기 위한 중요한 지표이다. 연구자들은 영상을 육안으로 분석하기 때문에 분석에 많은 시간과 고도의 집중력이 요구된다. 게다가 연구자의 주관적 관점이 분석에 개입되어 결과를 객관적으로 정량화하는데 어려움이 있다. 따라서 본 연구에서는 OpenCV 라이브러리를 이용하여 세포의 자동 분석을 위한 HCS(High Content Screen) 알고리즘을 개발하였다. HCS 알고리즘은 이미지 전처리 과정, 세포 계수, 세포 주기와 분열지수 분석 기능을 포함한다. 본 연구에서는 공초점 레이저 현미경을 통해 얻은 위암세포(MKN-28) 영상을 분석에 사용하였으며, 성능 평가를 위해 세포영상 분석 프로그램인 ImageJ와 전문 연구원의 세포 계수 분석결과를 비교하였다. 실험 결과 HCS 알고리즘의 평균 정확성이 99.7%로 나타났다.