• Title/Summary/Keyword: Mitotic Index

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Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

  • Kang, Sun Kyoung;Bae, Hyun Joo;Kwon, Woo Sun;Che, Jingmin;Kim, Tae Soo;Chung, Hyun Cheol;Rha, Sun Young
    • Genomics & Informatics
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    • v.18 no.4
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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.

Large Cell Neuroendocrine Carcinoma of the Extrahepatic Bile Duct (간외담도에 발생한 신경내분비암종 1예)

  • Park, Ji Young;Jeon, Tae Joo
    • The Korean Journal of Gastroenterology
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    • v.72 no.6
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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.

Effect of Brown Rice Extract on Mitomycin C-Induced Chromosome Aberration in Cultured CHL Cells (현미 추출물이 Mitomycin C로 유발된 CHL 세포의 염색체 이상에 미치는 영향)

  • Chun, Hyang-Sook;Kim, In-Ho;Kim, Hyun-Jung
    • Korean Journal of Food Science and Technology
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    • v.27 no.6
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    • pp.1003-1007
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    • 1995
  • The effect of brown rice extract on mitomycin C(MMC)-induced chromosome aberration was examined in cultured Chinese hamster lung(CHL) cells, after induction of chromosome aberration and mitotic index in CHL cells cultured with MMC were observed. There were no significant differences between mitotic indices of CHL cells treated with DMSO, and MMC and brown rice extract. The frequency of chromosome aberration showed dose-dependent relationship in CHL cells treated with $0.2{\sim}3.0\;{\mu}g$/assay of MMC. But chromosome aberrations could not be assayed Our to cytotoxicity of MMC when its concentrations were above $3.0\;{\mu}g$/assay. Chromatid type, especially gap and break, of chromosome aberration were most frequently observed. When CHL cells treated with $2.0\;{\mu}g$/assay of MMC and brown rice extracts of concentration ranging $0.75{\sim}10.0\;{\mu}g$/assay were incubated, frequencies of chromosome aberration induced by MMC were significantly decreased at above concentrations(p<0.01, p<0.05). As concentration of brown rice extract was increased, frequencies of chromosome aberration was decreased $7{\sim}30%$, in some irregularity.

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Characterization and Resistance Mechanisms of A 5-fluorouracil-resistant Hepatocellular Carcinoma Cell Line

  • Gu, Wei;Fang, Fan-Fu;Li, Bai;Cheng, Bin-Bin;Ling, Chang-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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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.

Clinicopathologic Features of Breast Carcinomas Classified by Biomarkers and Correlation with Microvessel Density and VEGF Expression: A Study from Thailand

  • Chuangsuwanich, Tuenjai;Pongpruttipan, Tawatchai;O-charoenrat, Pornchai;Komoltri, Chulaluk;Watcharahirun, Suwapee;Sa-nguanraksa, Doonyapat
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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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.

Biologic Effect of Non-ionizing Radiation (비전리방사선의 생물학적 작용)

  • Huh, Seung-Jae;Wu, Hong-Gyun
    • Journal of Radiation Protection and Research
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    • v.20 no.3
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    • pp.163-168
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    • 1995
  • The Radio-frequency electromagnetic(RFEM) spectrum is defined as waves that range in frequency from>0 to $3{\times}1012Hz$. Although there are several thousands of reports that present data or opinion of the biological response to RFEM radiation, no consensus has emerged regarding thresholds and mechanisms of injury. This review presents a overview of the subject on mechanisms of interaction of RFEM fields with tissue, chromosomal and mutagenic effect. carcinogenic effects. The scope of the review is expanded to include systemic effects such as those on reproduction, growth, and development, hematological effects. Some biological end points, those with associated with behavior and cataractogenesis is discussed.

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Influence of Ganyeumilhobang on Acute and Chronic Liver Injury in Experimental Animal (간염1호방(肝炎1號方)이 실험동물(實驗動物)의 급만성(急慢性) 간손상(肝損傷)에 미치는 영향(影響))

  • Choi, Su-Deock;Kim, Young-Jin;Kim, Kang-San
    • The Journal of Internal Korean Medicine
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    • v.19 no.1
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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.

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Cytologic Features of Papillary Immature Metaplasia of Uterine Cervix (유두상 미성숙 화생의 자궁경부 세포진 소견)

  • Kim, Hye-Sun;Seon, Mee-Im;Kim, Yee-Jung;Kim, Hy-Sook
    • The Korean Journal of Cytopathology
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    • v.13 no.1
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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.

Histopathological classification of the bovine lymphoma caused by bovine leukemia virus in Korea (소 백혈병 바이러스 감염에 의한 소 림프종의 병리조직학적 분류)

  • Yoon, Soon-Seek;Lee, Kyeong-Hyun;Bae, You-Chan;Jean, Young-Hwa;Kang, Mun-Il;Lee, O-Soo;Han, Hong-Ryul
    • Korean Journal of Veterinary Research
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    • v.45 no.3
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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.

Development of HCS(High Contents Screening) Software Using Open Source Library (오픈 소스 라이브러리를 활용한 HCS 소프트웨어 개발)

  • Na, Ye Ji;Ho, Jong Gab;Lee, Sang Joon;Min, Se Dong
    • KIPS Transactions on Software and Data Engineering
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    • v.5 no.6
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    • pp.267-272
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    • 2016
  • Microscope cell image is an important indicator for obtaining the biological information in a bio-informatics fields. Since human observers have been examining the cell image with microscope, a lot of time and high concentration are required to analyze cell images. Furthermore, It is difficult for the human eye to quantify objectively features in cell images. In this study, we developed HCS algorithm for automatic analysis of cell image using an OpenCV library. HCS algorithm contains the cell image preprocessing, cell counting, cell cycle and mitotic index analysis algorithm. We used human cancer cell (MKN-28) obtained by the confocal laser microscope for image analysis. We compare the value of cell counting to imageJ and to a professional observer to evaluate our algorithm performance. The experimental results showed that the average accuracy of our algorithm is 99.7%.