1.A Quantitative Analysis for Pre-processing Algorithm of Aberration Chromosome Observation.
Gye Rok JEON ; Yong Hoon CHANG ; Sang Hee EOM
Journal of Korean Society of Medical Informatics 2002;8(1):63-70
The task of chromosome analysis is the classification of human chromosomes. The feature parameter of chromosome is very important information for chromosome analysis. The special preprocessing algorithm is required to extracting them. In this paper, we performed quantitative analysis for preprocessing algorithm of observation of chromosomal aberrations. Two algorithms is used MAT and reconstruction. The morphological feature parameters were centromeric index(C.I.), relative length ratio(R.L.), relative area ratio(R.A.) and chromosome length(C.L.), and the density and width profiles. The reconstruction of chromosome images by this reconstruction algorithm was appeared as effective algorithms to observe and extract chromosome parameter.
Chromosome Aberrations
;
Chromosomes, Human
;
Classification
;
Humans
2.A Quantitative Analysis for Pre-processing Algorithm of Aberration Chromosome Observation.
Gye Rok JEON ; Yong Hoon CHANG ; Sang Hee EOM
Journal of Korean Society of Medical Informatics 2002;8(1):63-70
The task of chromosome analysis is the classification of human chromosomes. The feature parameter of chromosome is very important information for chromosome analysis. The special preprocessing algorithm is required to extracting them. In this paper, we performed quantitative analysis for preprocessing algorithm of observation of chromosomal aberrations. Two algorithms is used MAT and reconstruction. The morphological feature parameters were centromeric index(C.I.), relative length ratio(R.L.), relative area ratio(R.A.) and chromosome length(C.L.), and the density and width profiles. The reconstruction of chromosome images by this reconstruction algorithm was appeared as effective algorithms to observe and extract chromosome parameter.
Chromosome Aberrations
;
Chromosomes, Human
;
Classification
;
Humans
3.Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers
Jae Sik KIM ; Joo Ho LEE ; Sang-Rok JEON ; Yongsub KIM ; Seung Hyuck JEON ; Hong-Gyun WU
Cancer Research and Treatment 2023;55(3):737-745
Purpose:
Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen.
Materials and Methods:
Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction.
Results:
We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment.
Conclusion
The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.
4.Tumor Growth Suppression and Enhanced Radioresponse by an Exogenous Epidermal Growth Factor in Mouse Xenograft Models with A431 Cells.
Yu Jin LIM ; Sang Rok JEON ; Jae Moon KOH ; Hong Gyun WU
Cancer Research and Treatment 2015;47(4):921-930
PURPOSE: The purpose of this study was to evaluate whether an exogenous epidermal growth factor (EGF) could induce anti-tumor and radiosensitizing effects in vivo. MATERIALS AND METHODS: BALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cells in the right hind legs were divided into five groups: I (no treatment), II (EGF for 6 days), III (EGF for 20 days), IV (radiotherapy [RT]), and V (RT plus concomitant EGF). EGF was administered intraperitoneally (5 mg/kg) once a day and the RT dose was 30 Gy in six fractions. Hematoxylin and eosin (H&E) stained sections of tumor, liver, lung, and kidney tissues were investigated. Additionally, tumors were subjected to immunohistochemistry staining with caspase-3. RESULTS: EGF for 6 days decreased tumor volume, but it approached the level of the control group at the end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group V while the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20 days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistry revealed that mice in group V showed stronger intensity than those in group IV. There were no abnormal histological findings upon H&E staining of the normal organs. CONCLUSION: EGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431 cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design of fractionated irradiation.
Animals
;
Antineoplastic Agents
;
Apoptosis
;
Caspase 3
;
Eosine Yellowish-(YS)
;
Epidermal Growth Factor*
;
Follow-Up Studies
;
Hematoxylin
;
Heterografts*
;
Immunohistochemistry
;
Kidney
;
Leg
;
Liver
;
Lung
;
Mice*
;
Radiation-Sensitizing Agents
;
Tumor Burden
;
Xenograft Model Antitumor Assays
5.Synaptic Reorganization of Dentate Mossy Fibers and Expression of Calcium Binding Proteins in Hippocampal Sclerosis of Temporal Lobe Epilepsy.
Sang Pyo KIM ; Seung Pil KIM ; Seung Che CHO ; Young Rok CHO ; Ji Min JEON ; Yu Na KANG ; Kun Young KWON ; Eun Sook CHANG
Korean Journal of Pathology 1998;32(5):328-336
This study was designed to identify expression of calcium-binding proteins and synaptic reorganizations of dentate mossy fibers in hippocampal sclerosis of human temporal lobe epilepsy. Hippocampal neuronal density was quantitively analyzed in temporal lobe epilepsy group (n=50) to investigate the degree of hippocampal sclerosis and it was compared with that of autopsy control (n=3). To verify the distribution of calcium-binding proteins in neurons of epileptic hippocampi, the parvalbumin (PV)-immunoreactive and calbindin-D28K (CB)-immunoreactive neurons were quantitively analyzed in each area of Ammon's horn by immunohistochemical stain. Also, to clarify synaptic reorganizations of the dentate mossy fibers, a part of each hippocampus was examined under light microscopy and transmission electron microscopy using Timm sulphide silver method. In epileptic hippocampi, severity of hippocampal sclerosis (HS) was graded four, which consisted of 3 cases with no HS, 6 mild HS, 12 moderate HS, and 29 severe HS. The hippocampal neuronal loss was most prominent in CA1, followed by CA4 and CA2. Expression of calcium-binding proteins was more prevalent in CA2 of all groups. The proportion of PV-immunoreactive neurons in CA1 and CA4 significantly increased in the moderate and severe HS group, whereas the proportion of CB-immunoreactive neurons did not correlated with the severity of HS. Timm granules were noted in inner molecular supragranular layer of dentate gyrus of epileptic hippocampi and they tended to increase in proportion along with the severity of hippocampal sclerosis. Transmission electron microscopy showed that supragranular Timm granules corresponded to synaptic terminals of mossy fibers. These results suggest that parvalbumin appears to have more protective effect against neuronal loss and that mossy fiber synaptic reorganization seems to play a major role in pathogenesis of hippocampal sclerosis of human temporal lobe epilepsy.
Autopsy
;
Calbindin 1
;
Calcium*
;
Calcium-Binding Proteins*
;
Dentate Gyrus
;
Epilepsy, Temporal Lobe*
;
Hippocampus
;
Humans
;
Microscopy
;
Microscopy, Electron, Transmission
;
Nerve Fibers, Myelinated
;
Neurons
;
Presynaptic Terminals
;
Sclerosis*
;
Silver
;
Temporal Lobe*
6.Measurement of Regional Cerebral Blood Volume in Normal Rabbits on Perfusion-weighted MR Image.
Byeong Rae PARK ; Soo Young YEO ; Sang Ok NA ; Hak Jin KIM ; Seok Hong LEE ; Gye Rok JEON
Journal of the Korean Society of Magnetic Resonance in Medicine 2000;4(2):100-106
PURPOSE: To evaluate the usefulness of cerebral blood flow measurement applied to perfusion weighted image with short-scan time single shot gradient echo-planar technique in measuring cerebral blood volume(rCBV) of normal rabbits. MATERIALS AND METHODS: With 2.1-3.6 kg weighted rabbits, image is acquired when they are in supine position in children positioner. Perfusion weighted image is acquired to 44 seconds per 1 second successively. After 4 seconds later, Gd-DTPA 2ml are injected into int. jugular vein with 2 ml per second and normal saline is also injected after that. Same technique is applied 2 times per 30 minites in same rabbit. After Image is obtained in two part of cerebral cortex at vertex, convexity, in one of basal ganglia with choosing about 3-5mm2 areas. Curve of signal intensity changes in time sequence is drawn. After this images are transmitted by PC and software IDL, regional cerebral blood volume is measured with imaging processing program made by us. RESULTS: With 22 of 24 rabbits, satisfactory 1-2 signal intensity versus time curve is made. Cerebral blood capacity and contrast media stay time (ST) is measured in two cerebral cortex and basal ganglia refering in parietal cerebral cortex. Mean focal cerebral blood flow capacity ratio in cortex was 0.97+/-0.35 and in basal ganglia, 0.99+/-0.37, mean contrast media stay time in cortex was 9.83+/-1.63 sec and in basal ganglia, 9.42+/-1.14 sec, but there was no statistically significant difference between two areas (p=0.05). CONCLUSION: In cerebral cortex and basal ganglia, there is no difference in mean focal blood volume and mean contrast stay time. Therefore, PWI is useful in cerebral blood flow and early diagnosis, prognosis of cerebral ischemic disease. Hereafter, it is helpful in analysing cerebral blood flow changes with comparison difference in rCBV between normal tissue and ischemic tissue, and that with DWI finding in infarcted patient.
Basal Ganglia
;
Blood Volume*
;
Cerebral Cortex
;
Child
;
Contrast Media
;
Early Diagnosis
;
Gadolinium DTPA
;
Humans
;
Jugular Veins
;
Perfusion
;
Prognosis
;
Rabbits*
;
Rabeprazole
;
Supine Position
7.Influence of Delayed Gastric Emptying in Radiotherapy after a Subtotal Gastrectomy.
Dong Hyun KIM ; Won Taek KIM ; Mi Ran LEE ; Yong Gan KI ; Ji Ho NAM ; Dal PARK ; Ho Sang JEON ; Kye Rok JEON ; Dong Won KIM
The Journal of the Korean Society for Therapeutic Radiology and Oncology 2009;27(4):194-200
PURPOSE: This aim of this study was to evaluate changes in gastric volume and organ position as a result of delayed gastric emptying after a subtotal gastrectomy performed as part of the treatment of stomach cancer. MATERIALS AND METHODS: The medical records of 32 patients who underwent concurrent chemoradiotherapy after a subtotal gastrectomy from March 2005 to December 2008 were reviewed. Of these, 5 patients that had more than 50 cc of residual gastric food detected at computed tomography (CT) simulation, were retrospectively enrolled in this study. Gastric volume and organ location was measured from CT images obtained before radiotherapy, twice weekly. In addition, authors evaluated the change of radiation dose distribution to planning the target volume and normal organ in a constant radiation therapy plan regardless of gastric volume variation. RESULTS: A variation in the gastric volume was observed during the radiotherapy period (64.2~340.8 cc; mean, 188.2 cc). According to the change in gastric volume, the location of the left kidney was shifted up to 0.7 - 2.2 cm (mean, 1.2 cm) in the z-axis. Under-dose to planning target volume (V43, 79.5+/-10.4%) and over-dose to left kidney (V20, 34.1+/-12.1%; Mean dose, 23.5+/-8.3 Gy) was expected, given that gastric volume change due to delayed gastric emptying wasn't taken into account. CONCLUSION: This study has shown that a great change in gastric volume and left kidney location may occur during the radiation therapy period following a subtotal gastrectomy, as a result of delayed gastric emptying. Detection of patients who experienced delayed gastric emptying and the application of gastric volume variation to radiation therapy planning will be very important.
Chemoradiotherapy
;
Gastrectomy
;
Gastric Emptying
;
Humans
;
Kidney
;
Medical Records
;
Retrospective Studies
;
Stomach Neoplasms
8.Vancomycin-Resistant Enterococcal Bacteremia in a Hematology Unit: Risk Factors for Mortality and Impact of Adequate Antimicrobial Therapy on Mortality.
Jae Bum JUN ; Seong Ho CHOI ; Sang Rok LEE ; Min Hyuk JEON ; Hyun Hee KWON ; Sang Oh LEE ; Sang Ho CHOI ; Jun Hee WOO ; Yang Soo KIM
Infection and Chemotherapy 2007;39(3):133-141
BACKGROUND: Vancomycin resistant enterococcal (VRE) bacteremia is increasing among patients with hematologic malignancies. Our study was to determine the clinical characteristics, risk factors for mortality, and effect of adequate antimicrobial therapy on outcome in patients with hematologic malignancies who developed VRE bacteremia. MATERIALS AND METHODS: we retrospectively reviewed episodes of VRE bacteremia in 90 patients with hematologic malignancices from January 1997 to December 2006. Adequate antimicrobial therapy was defined as the use of linezolid or quinupristin/dalfopristin, initiated within 72 hours of initial positive blood culture and continuing for at least 48 hours. Outcome was evaluated at 14 and 28 days after onset of bacteremia. RESULTS: The overall 14-day and 28-day mortality rates were 44.4% (40/90) and 54.4% (49/90) respectively. Failure of neutrophil recovery (odds ratio [OR], 40.29; 95% confidence interval [CI], 6.22 to 260.72; P< or =0.001) and increased APACHE II score (OR, 1.30; 95% CI, 1.07 to 1.58; P=0.008) were independent risk factors for 14-day as well as for 28-day mortality. To specifically examine the effects of adequate antimicrobial therapy, we performed a separate analysis of the 14-day mortality, after excluding 6 patients who died within 48 hours of bacteremia onset. Multivariate analysis showed that failure of neutrophil recovery (OR, 42.10; 95% CI, 5.77 to 307.00; P< or =0.001) and increased APACHE II score (OR, 1.25; 95% CI, 1.02 to 1.53; P=0.026) were still independently associated with mortality. Adequate antimicrobial therapy, however, did not have a protective effect (OR, 1.91; 95% CI, 0.50 to 7,22; P= 0.338). Of the 65 patients with monomicrobial bacteremia, 30 (46.2%) received adequate antimicrobial therapy and 35 (53.8%) did not: their 14-day mortality rates were 40.0% (12/30) and 42.9% (15/35), respectively (P=0.816). CONCLUSION: In conclusion, severity of underlying illness was associated with mortality. Adequacy of antimicrobial therapy did not improve survival, this may be due to low virulence of enterococci and severity of underlying disease.
APACHE
;
Bacteremia*
;
Enterococcus
;
Hematologic Neoplasms
;
Hematology*
;
Humans
;
Linezolid
;
Mortality*
;
Multivariate Analysis
;
Neutrophils
;
Retrospective Studies
;
Risk Factors*
;
Vancomycin
;
Virulence
9.Vancomycin-Resistant Enterococcal Bacteremia in a Hematology Unit: Risk Factors for Mortality and Impact of Adequate Antimicrobial Therapy on Mortality.
Jae Bum JUN ; Seong Ho CHOI ; Sang Rok LEE ; Min Hyuk JEON ; Hyun Hee KWON ; Sang Oh LEE ; Sang Ho CHOI ; Jun Hee WOO ; Yang Soo KIM
Infection and Chemotherapy 2007;39(3):133-141
BACKGROUND: Vancomycin resistant enterococcal (VRE) bacteremia is increasing among patients with hematologic malignancies. Our study was to determine the clinical characteristics, risk factors for mortality, and effect of adequate antimicrobial therapy on outcome in patients with hematologic malignancies who developed VRE bacteremia. MATERIALS AND METHODS: we retrospectively reviewed episodes of VRE bacteremia in 90 patients with hematologic malignancices from January 1997 to December 2006. Adequate antimicrobial therapy was defined as the use of linezolid or quinupristin/dalfopristin, initiated within 72 hours of initial positive blood culture and continuing for at least 48 hours. Outcome was evaluated at 14 and 28 days after onset of bacteremia. RESULTS: The overall 14-day and 28-day mortality rates were 44.4% (40/90) and 54.4% (49/90) respectively. Failure of neutrophil recovery (odds ratio [OR], 40.29; 95% confidence interval [CI], 6.22 to 260.72; P< or =0.001) and increased APACHE II score (OR, 1.30; 95% CI, 1.07 to 1.58; P=0.008) were independent risk factors for 14-day as well as for 28-day mortality. To specifically examine the effects of adequate antimicrobial therapy, we performed a separate analysis of the 14-day mortality, after excluding 6 patients who died within 48 hours of bacteremia onset. Multivariate analysis showed that failure of neutrophil recovery (OR, 42.10; 95% CI, 5.77 to 307.00; P< or =0.001) and increased APACHE II score (OR, 1.25; 95% CI, 1.02 to 1.53; P=0.026) were still independently associated with mortality. Adequate antimicrobial therapy, however, did not have a protective effect (OR, 1.91; 95% CI, 0.50 to 7,22; P= 0.338). Of the 65 patients with monomicrobial bacteremia, 30 (46.2%) received adequate antimicrobial therapy and 35 (53.8%) did not: their 14-day mortality rates were 40.0% (12/30) and 42.9% (15/35), respectively (P=0.816). CONCLUSION: In conclusion, severity of underlying illness was associated with mortality. Adequacy of antimicrobial therapy did not improve survival, this may be due to low virulence of enterococci and severity of underlying disease.
APACHE
;
Bacteremia*
;
Enterococcus
;
Hematologic Neoplasms
;
Hematology*
;
Humans
;
Linezolid
;
Mortality*
;
Multivariate Analysis
;
Neutrophils
;
Retrospective Studies
;
Risk Factors*
;
Vancomycin
;
Virulence
10.Telomerase Activity in Primary Lung Cancers.
Sang Myung YUN ; Kyung Rok KWAK ; Jee Yoon HWANG ; Sam Seok PARK ; Doo Soo JEON ; Cheol Min KIM ; Min Ki LEE ; Soon Kew PARK
Tuberculosis and Respiratory Diseases 1999;46(2):195-203
BACKGROUND: Telomerase enzyme activity is not detected in most normal cells, a phonomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumor, including lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of malignant phenotype. In this study, we determined whether telomerase activity was associated with tumor pathologic stage. METHODS: Primary tumor specimens obtained by bronchoscopic biopsies from 33 patients were analyzed. Telomerase activity was measured by means of a modified Telomeric Repeat Amplication Protocol(TRAP) assay. RESULTS: Telomerase activity was detected in 23 of the 27 non small cell lung cancer and 5 of 6 small cell lung cancer. A few primary tumors did not appear to have detectable telomerase activity. Positive associations were found between the telomerase-positive rate and tumor stage(p<0.05). CONCLUSION: High telomerase activity is detected frequently in primary lung cancers that exhibit high tumor cell proliferation rates and advanced pathologic stage.
Biopsy
;
Cell Proliferation
;
Humans
;
Lung Neoplasms*
;
Lung*
;
Phenotype
;
Small Cell Lung Carcinoma
;
Telomerase*
;
Telomere