• Journal of Life Science
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• v.24 no.12
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• pp.1339-1344
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• 2014

Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

• Neonatal Medicine
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• v.17 no.1
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• pp.64-74
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• 2010

Purpose : The aim of this study was to determine the risk factors, clinical characteristics and prognosis for the development of periventricular leukomalacia (PVL) in preterm infants according to the extent and site of the PVL. Methods : The medical records of infants (under 36 weeks of gestational age) delivered from January 1999 to December 2008 were reviewed. Twenty-five preterm infants with were PVL were diagnosed by brain magnetic resonance imaging (MRI) and an addition 50preterm infants with no brain lesions were enrolled in this study. The perinatal and neonatal risk factors for the development of PVL was determine in these infants. Mental and Psychomotor Developmental Indices (MDI, PDI) were assessed by a clinical psychologist using the Bayley Scales of Infant Development II. We compared the differences of the clinical characteristics and prognosis according to brain MRI findings. Results : Maternal fever, young maternal age, extended oxygen use, hypotension within the first week of birth, use of inotropics within the first week of birth, and respiratory distress syndrome were the risk factors associated with PVL (P <0.05). In the multivariate analysis, maternal fever and extended oxygen use were statistically significant independent risk factors (P <0.05). The mean MDI and PDI scores of the PVL group (74.4$\pm$ 27.8 and 58.0$\pm$17.7) were significantly lower than those of the control group (103.5$\pm$8.9 and 101.7$\pm$16.1, P <0.05). Conclusion : Maternal fever and extended oxygen use were independent risk factors for PVL. We should pay attention to infants who had the risk factors and follow them up closely by brain imaging study and Bayley Scales of Infant Development II.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.402-410
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• 2009

Purpose: The aim of this study was to determine the incidence and malignant rate of incidental asymmetric palatine tonsillar uptake (ATU) on $^{18}F$-FDG PET/CT in various clinical indications and to evaluate the clinical and PET/CT findings suggesting malignancy. Materials and Methods: We retrospectively reviewed a total of 2,901 patients ($58.4{\pm}12.3$ yrs, range 20~88 yrs, M:F = 1,841:1,060) who underwent $^{18}F$-FDG PET/CT during an 1-year period with various indications except primary tonsillar cancer and lymphoma evaluation. On $^{18}F$-FDG PET/CT, metabolic abnormality of the palatine tonsil and cervical lymph node were visually assessed. ATU was defined as increased palatine tonsillar uptake with diffuse, focal, or irregular pattern compared to contralateral side. The incidence and malignant ratio of ATU were evaluated according to clinical and PET/CT findings. Results: Of 2,901 cases, 290(10,0%) showed ATU. The incidence of ATU showed seasonal variation and was high in the winter (12.1%). Of 209 cases with ATU confirmed pathologically and/or clinically, five (2.4%) were malignant lesions. ATU with irregular uptake pattern (2/2) and in cases referred for cervical lymph node metastasis of unknown origin (3/5) were frequently associated with malignant lesion (p<0.05). Conclusion: ATU was not infrequently observed on $^{18}F$-FDG PET/CT, and the malignant risk of ATU was low. However, ATU with cervical lymph node metastasis or with irregular pattern on PET/CT would be further evaluated by the histopathologic examination.

• Journal of Radiation Protection and Research
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• v.38 no.4
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• pp.214-227
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• 2013

Computed tomographic scan as a screening procedures in asymptomatic individuals has seen a steady increase with the introduction of multiple-raw detector CT scanners. This report provides a brief review of the current controversy surrounding CT cancer screening, with a focus on the radiation induced cancer risks and clinical efficacy. 1. A large study of patients at high risk of lung cancer(the National Lung Screening Trial[NLST]) showed that CT screening reduced cancer deaths by 20%(1.33% in those screened compared with 1.67% in those not screened). The rate of positive screening tests was 24.2% and 96.4% of the positive screening results in the low-dose CT group were false-positive. Radiation induced lung cancer risk was estimated the most important in screening population because ERR of radiation induced lung cancer does not show the decrease with increasing age and synergistic connection between smoking and radiation risk. Therefore, the radiation risk may be on the same order of magnitude as the benefit observed in the NLST. Optimal screening strategy remain uncertain, CT lung cancer screening is not yet ready for implementation. 2. Computed tomographic colonography is as good as colonoscopy for detecting colon cancer and is almost as good as colonoscopy for detecting advanced adenomas, but significantly less sensitive and specific for smaller lesions and disadvantageous for subsequent therapeutic optical colonoscopy if polyps are detected. The average effective dose from CT colonography was estimated 8-10 $mS{\nu}$, which could be a significant dose if administered routinely within the population over many years. CT colonography should a) achieve at least 90% sensitivity and specificity in the size category from 6 and 10 mm, b) offer non-cathartic bowl preparation and c) be optimized and standardized CT parameters if it is to be used for mass screening. 3. There is little evidence that demonstrates, for whole-body scanning, the benefit outweighs the detriment. This test found large portion of patient(86~90.8%) had at least one abnormal finding, whereas only 2% were estimated to have clinically significant disease. Annual scans from ages 45 to 75 years would accrue an estimated lifetime cancer mortality risk of 1.9%. There is no group within the medical community that recommends whole-body CT. No good studies indicate the accuracy of screening CT, at this time. The benefit/risk balance for any of the commonly suggested CT screening techniques has yet to be established. These areas need further research. Therefore wild screening should be avoided.

• Journal of Life Science
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• v.18 no.1
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• pp.16-22
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• 2008

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.525-532
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• 1999

The parathyroid hormone related protein (PTHrP) is the most common causative peptide of humoral hypercalcemia of malignancy. In contrast, the serum level of parathyroid hormone (PTH) is low to undetectable in the majority of patients with malignancy associated hypercalcemia. Few cases exist in which the production and secretion of PTH by malignant nonparathyroid tumors have been authenticated. To our knowledge, there is very rare case in which a nonparathyroid tumor expressed simultaneously both the PTH and PTHrP. We report a case of squamous cell carcinoma of the lung with hypercalcemia which presented with simultaneous elevation of serum PTH and PTHrP. Severe hypercalcemia (serum calcium, 7.5 mEq/L) was found in a 65-year-old man who had a squamous cell carcinoma of the lung without any bony metastasis and detectable parathyroid abnormalities on isotope scintigraphy. The serum level of intact parathyroid hormone (PTH) con centration was markedly elevated as measured in two site radioimmunoreactive PTH assays (intact PTH 150 pg/mL ; normal 9~55). The serum level of a PTHrP was also increased as measured in C-terminal region specific radioimmunoassay (PTHrP 99.1 pmol/L; normal 13.8~55.3). There are no evidences of coincidental primary hyperparathyroidism in parathyroid MIBI scan and other imaging studies including neck ultrasonography and computed tomography. These results suggest that simultaneous elevation of serum PTH and PTHrP in this patient can be caused by production of both PTHrP and PTH in other nonparathyroid lesions such as squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.198-206
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• 2000

Background : Pulmonary complications following bonemarrow transplantation (BMT) are common and associated with a high mortality rate. We investigated the yield, safety, and impact of fiberoptic bronchoscopy (FOB) for diagnosis of postBMT pneumoniae. Methods : From May 1997 to April 2000, 56 FOBs were performed in 52 post BMT patients for clinical pneumoniae. BMT patients with respiratory symptoms and/or pulmonary infiltrates had a thoracic HRCT(high resolution computed tomography) and bronchoscopic examination including BAL (bronchoalveolar lavage), TBLB (transbronchial lung biopsy), PSB (protected specimen brush). Results : The characteristics of the subjects were as follows : 37 males, 15 females, mean age of 31.3 years(l7-45), 35 sibling donor allogenic BMTs, 15 nonrelated donor allogenic BMTs, and 2 autologous BMTs. Fiftynine percent of FOBs (33 FOBs, 31 patients) were diagnostic. Isolated pathogens included the following : 12 cytomegalovirus (CMV) (21.4 %), 7 pneumocystis carinii (PC) (12.5 %), 11 CMV with PC (19.6 %), 2 Mycobacaterium tuberculosis (3.6%), and 1 streptococcus (1.8%). Most of the radiographic findings were diffuse interstitial lesions. CMV pneumoniae had mainly diffuse interstitial nodular lesion, and PC pneumoniae had diffuse, interstitial ground glass opacity(GGO). When CMV was accompanied by PC, a combined pattern of nodular and GGO was present. Of the 56 cases (23.2%), 13 died of CMV pneumoniae (n=2), PCP (n=2),mixed infection with CMV and PC (n=3), underlying GVHD (n=1), underlying leukemia progression (n=1), or respiratory failure of unknown origin (n=4). There was no major complication by bronchoscopy. Only 3 cases developed minor bleeding and 1 episode temporary hypoxemia. Conclusion : Based on our findings, CMV and PC are the major causes of postBMT pneumoniae. In addition, BAL can be considered a safe and accurate procedure for the evaluation of pulmonary complications after BMT.

• Investigative Magnetic Resonance Imaging
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• v.13 no.1
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• pp.81-87
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• 2009

Purpose : We sought to evaluate enhancement of plaque with gadolinium-based contrast agent by magnetic resonance imaging (MRI) in comparison with histopathology, namely lipid-rich and macrophage-rich components that were two representative characteristics of plaque vulnerability using atherosclerotic rabbit aorta in order to determine which histopathologic component is relevant to the enhancement. Materials and Methods : New Zealand white rabbit (n=4, weight 3.0 to 3.5 kg, all male) was used for animal model of atherosclerosis. Atherosclerotic aortic lesions were induced by high-cholesterol diet and double balloon injury. T1-weight axial images were acquired before and after gadolinium-based contrast agent using a 3-T MRI. MR images and the matched histopathological sections (n=35) were divided into 4 quadrants or 3 (n=130). Enhancement ratio (ER, ER=SIpost/SIpre) on MRI was calculated for each quadrant and compared with histopathology in regard to lipid-rich and macrophage-rich areas. Results : Lipid-rich quadrants were 72 and fibrous quadrants were 58. The number of quadrants which had macrophage-rich areas was 105 and that of quadrants which did not have macrophage-rich areas was 25. ER was significantly higher in lipid-rich quadrants than in fibrous quadrants (mean ER 2.25c$\pm$0.41 vs. 2.72$\pm$0.65, p=0.013). ER poorly correlated with macrophage-rich areas when lipid-component was controlled (correlation coefficient -0.203, p=0.236). Conclusion : Lipid-rich plaques showed stronger enhancement than fibrous plaques using a standard gadolinium-based extracellular contrast agent. Macrophage infiltration did not correlate with degree of enhancement. Further study is warranted that account for optimal time of imaging after contrast injection using various plaque models from early to advanced stages and all possible parameters associated with contrast enhancement.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.15-20
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• 2005

Purpose: Physiologic intestinal FDG uptake is frequently observed in asymptomatic individuals for cancer screening FDG PET Colonic FDG accumulation is a well-known confusing findings that interfere true cancer detection or cause false positive. The aim of this study was to evaluate the pattern and intensity of colonic uptake in whole body FDG PET in asymptomatic healthy adults and to correlate them with colonoscopic findings. Materials and Methods: We reviewed retrospectively 64 subjects (age: 27-87, M:F=31:33) who underwent both FDG PET and colonoscopy for cancer screening. FDG uptake patterns were classified as focal, segmental and diffuse. Maximum SUV were measured. The PET results were compared with colonoscopic and histologic findings. Results: In 13 patients FDG bowel uptake was interpreted as focal, in 17 patients as segmental and in 34 patients as diffuse uptake. Six adenomas (17.6%, average diameter=5.0 mm) were found in diffuse pattern, 7 adenomas (41.1%, 5.6 mm) in segmental and 4 adenomas and 1 adenocarcinoma (38.5%, 16.4 mm) in focal uptake pattern. In patients with focal uptake, four were non-adenomatous pathologic lesions (30.8%, 2 intestinal tuberculosis, 2 mucosal ulcer). There is no difference of mean SUV between patients with adenoma and with negative colonoscopic results in each group of intestinal FDG pattern (Diffuse: $1.7{\pm}0.1\;vs.\;1.9{\pm}0.5$, Segmental: $4.8{\pm}3.6\;vs.\;4.2{\pm}1.2$, Focal: $6.5{\pm}4.7\;vs.\;3.5{\pm}1.3$). large adenomas (>1 cm) can be detected more in the focal uptake pattern (4 out of 5) rather than in segmental (1 out of 7) or diffuse uptake (none) and had higher SUV ($6.3{\pm}4.8$) than small adenomas ($3.5{\pm}3.0$) (statistically insignificant). Conclusion: focal FDG uptake is associated more often with large adenoma and other pathologic findings in colonoscopy. Segmental uptake cannot discriminate presence of adenoma from negative results, while diffuse pattern may have more chance to be normal.

• Journal of Korean Neurosurgical Society
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• v.64 no.6
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• pp.983-994
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• 2021

Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.