• Radiation Oncology Journal
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• v.19 no.4
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• pp.335-344
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• 2001

Purpose : The aim of this study was to clarify the role of VEGF expression as an independent prognostic factor and to identify the patients at high risk for poor prognosis in stage IB cervical cancer. Materials and methods : A total of 118 patients with stage IB cervical cancer who had radical hysterectomy and pelvic lymph node dissection were included in the study. All known high risk factors of the patients were pathologically confirmed from the surgical specimen. Of the 118 patients, n patients were treated with postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded specimens of post-hysterectomy surgical materials. A semiquantitative analysis was made using a scoring system of 0, +, ++, and +++ for increasing intensity of stain. We classified the patients with scores from 0 to ++ as low VEGF expression and the patients with a score of +++ as high VEGF expression. Results : Of the 118 patients, 35 patients $(29.7\%)$ showed high VEGF expression. Strong correlations were found between the high VEGF expression and both deep stromal invasion (p=0.01) and the positive pelvic node (p=0.03). The 5-year overall and disease-free survival rates for all 118 patients were $95.5\%\;and\;93.8\%$. The 5-year overall (p=0.03) and disease-free survival (p<0.001) rates were $98.5\%\;and\;100%$ for low VEGF expression (0, +, and ++) and $85.5\%\;and\;79.7\%$ for high VEGF expression, respectively. Pelvic and distant failures for low versus high VEGF expression were $1.2\%$ versus $17.1\%$, (p=0.001) and $0\%$ versus $14.3\%$ (p<0.001), respectively. In a Cox multivariate analysis of survival, the high VEGF expression (p=0.02) and the bulky mass (p=0.02) were significant prognostic factors for overall survival. The high VEGF expression (p=0.002), and bulky mass (p=0.01) demonstrated as significant prognostic indicators for disease free survival. Conclusion : These results showed that VEGF expression was a highly significant predictor for pelvic and distant failure and the most significant prognostic factor of overall and disease free survival for the patients with stage IB cervix cancer treated with radical surgery. We strongly suggest that the immune-histochemistry for VEGF expression be performed in a routine clinical setting in order to identify the patients at high risk for poor prognosis in early stage cervical cancer. Furthermore, postoperative and/or chemotherapy did not reduce the pelvic failure and distant metastasis. To improve the cure rate for the patients with high VEGF expression in stage IB cervical cancer, antiangiogenic therapy including anti-VEGF Ab may be new treatment option.

• Journal of Chest Surgery
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• v.29 no.11
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• pp.1173-1181
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• 1996

The causes of degenerative changes in allograft cardiac valves are not well known to this day. Today's preserved allografts possess highly viable endothelial cells and degeneration of allografts can be facilitated by immune reaction which may be mediated by these viable cells. To test the antigenicity of endothelial cells, pieces from aortic wall were obtained from fresh and cryo-preserved rat allograft. Timings of sampling were prior to sterilization, after sterilization, after 1, 2, 7, 14 days of fresh preservation and cryopreservation. Endothelial cells were tested by immunohistochemical methods using monoclonal antibodies to MHC class I(MRC OX-18), class II(MRC OX-6) and ICAM-1 antigens. After transplantation of each group of aortic allograft at the subcutaneous layers of rats, population of CD4$^{+}$ T cell and CD8$^{+}$ T cell were analyzed with monoclonal antibodies after 1, 2, 3, 4, 6 and 8 weeks. MHC class I expression was 23.95% before preservation and increased to 35.53~48.08% after preservation(p=0.0183). MHC Class II expression was 9.72% before preservation and 10.13~13.39% after preservation(P=0.1599). ICAM-1 expression was 15.02% before preservation and increased to 19.85~35.33% after preservation(P=0.001). The proportion of CD4$^{+}$ T-cell was 42.13% before transplantation. And this was 49.23~36.8% after transplantation in No treat group (p=0.955), decreased to 29.56~32.80% in other group(p=0.0001~0.008). In all the groups, the proportion of CD8$^{+}$ T-cell increased from 25.57% before transplantation to 42.32~58.92% after transplantation(p=0.000l~0.0002). The CD4$^{+}$/CD8$^{+}$ ratio decreased from 1.22~2.28 at first week to 0.47~0.95 at eighth week(p=0.0001). The results revealed that the expression of MHC class I and ICAM-1 in aortic allograft endothelium were increased but that of MHC class II were not changed, despite the different method of preservation. During 8 weeks after transplantation of aortic allograft, the subpopulations of CD4$^{+}$ T cell were not changed or only slightly decreased but those of CD8$^{+}$ T cell were progressively increased.ely increased.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4773-4780
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• 2014

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

• Journal of Gastric Cancer
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• v.4 no.4
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• pp.207-212
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• 2004

Purpose: Invasion and metastasis in solid tumors require the action of tumor-associated proteases. The serine protease urokinase-type plasminogen (uPA) and receptor (uPAR) appear to have a major function in these processes. Expression of the uPAR is elevated in breast and colon carcinomas, and this is often associated with invasiveness and poor prognosis. The purpose of this study was to determine whether the expression of the uPAR gene correlates with clinico-pathological parameters in human gastric carcinomas. Materials and Methods: We examined the expression of uPAR mRNA by using northern blot analysis and RT-PCR in 35 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumor findings and survival rates were obtained from the patient records and from endoscopic, surgical, and pathological reports. Results: The expression of uPAR and was higher in most neoplasms than in the corresponding normal mucosal tissue. uPAR mRNA expression in tumors correlated well with lymph-node metastasis (P<0.02) and tumor stage (P<0.01). The survival rate of patients with tumors displaying high uPAR expression levels was significantly lower (P<0.04) than that of patients without uPAR expression, but IL-8 showed only the tendency of survival difference. Conclusion: These results suggest that uPAR may be an important prognostic factor in human gastric carcinomas.

• Journal of agricultural medicine and community health
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• v.27 no.1
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• pp.115-123
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• 2002

Objective: The aim of this study was to evaluate the patterns of helicopter emergency medical services (HEMS) in Ullung Island. Methods : The authors reviewed the records from emergency room diaries and the lists of helicopter transfers in the Ullung Public Health Medical Center over the 5-year period from Jan 1, 1997 to Dec 31, 2001. Results : One hundred thirteen cases were transferred by helicopters in 88 flights. According to year, the number of flights was 13(14.8%) and the number of cases was 15(13.3%) in 1997; 17(19.3%) and 21(18.6%) in 1998; 18(20.5%) and 20(17.7%) in 1999; 17(19.3%) and 20(17.7%) in 2000; and 23(26.1%) and 37(32.7%) in 2001. According to the kind of helicopter, the number of flights was 46(52.3%) and the number of cases was 60(53.1%) by Maritime police; and 19(21.6%) and 28(25.1%) by 119 rescue. According to time zone, there were no night flights. According to sex and age, there were 75 male cases(66.4%) and 28 cases(28.3%) of patients aged sixty years and over. The number of flights was 11(12.5%) and the number of cases was 15(13.3%) in November; 10 flights(11.4%) and 14 cases(12.4%) in March; and 7 cases(8.0%) in each of September, October and April. The most common season of helicopter transfer cases was autumn. According to transfer area, there were 48 cases (42.5%) in Pohang city, Gyeonsangbukdo; 35(31.0%) in Gangnung city, Gangwondo; and 17(15.0%) in Daegu metropolitan city. According to condition, there were 27 cases(23.9%) of cerebro-vascular accident, 13(11.5%) of fracture and 11(9.7%) of head injury. According to admission department, there were 42 cases(37.2%) in Neurosurgery, 21(18.6%) in Internal Medicine and 13(11.5%) in Orthopedic Surgery. According tothe Korea Standard Classification of Disease(3-KSCD), circulatory systemic disease(IX) and injury, intoxication and others (XIX) were the two most frequent categories with 34 cases(30.1%) each, followed by digestive system disease (XI) with 23 cases(20.4%). Conclusions : HEMS in Ullung Island leave much to be desired. Helicopters cannot make a night flight and are not equipped with medical facilities. HEMS in islands such as Ullung Island are essential. We hope that night flights, equipment-monitoring systems for emergency patients in the helicopters, and a law related to HEMS in the island will all be established.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.1
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• pp.101-104
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• 2010

Purpose: Raynaud scan is divided to flow, blood pool and local-delay image. Usually, we evaluate comparison through blood pool and local-delay image. We will evaluate about usability when comparative observe blood image and local-delay image in Raynaud scan that used $^{201}Tl$ as making flow image to one sheet of images. Materials and Methods: We have selected 29 Raynaud phenomenon patients aged 14~68 years who visited department of vascular surgery between Feb. 2008 and Aug. 2009. An intravenous injection $^{201}Tl$ of 111 MBq (3 mCi) to opposite side diagonal line limbs above an internal auditing department. Equipment used Philips gamma camera forte A-Z, and collimator used LEHR. Matrix size set up to each $64{\times}64$, $128{\times}128$, $256{\times}256$ and zoom factor used to full field. Protocol of dynamic is 2 second to 155 frames. Blood pool and delay count to 300 second. We set up ROI by a foundation to data acquired in PEGASYS processing program. Each results were analyzed with the SPSS 12.0 statistical software. Results: Each averages of count ratio (Rt / Lt) to have been given at composite image, a blood pool image, delay images analyzed at Raynaud phenomenon patients is $1.25{\pm}0.39$, $1.20{\pm}0.33$, $1.11{\pm}0.17$. The sample analysis results of blood pool image and delay image contented itself with p<0.029. Also, there don't have been each difference, and blood pool image, delay image regarding composite image was able to know. Conclusion: We were able to give help for comparison to evaluate a blood pool image and a local delay image at the Raynaud scan which used $^{201}Tl$ while making a flow image to one sheet image. Identification to be visual too was possible. If you are proceeded a researcher that there was further depth, you are more appropriate for, and you may get useful information.

• Journal of Korean Neurosurgical Society
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• v.30 no.9
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• pp.1094-1102
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• 2001

Objective : During the trans-condylar or trans-jugular approach for the lesion of cranio-cervical junction(CCJ), its necessary to identify the accurate locations of vertebral artery(VA), internal jugular vein(IJV) and its related lower cranial nerves. These neurovascular structures can also be damaged during the operation for vascular tumor or traumatic aneurysm around extra-jugular foramen, because of their changed locations. To reduce the neurovascular injury at the operation for CCJ, morphometric relationship of its surrounding neurovascular structures based on the tip of the transverse process of atlas(C1 TP), were studied. Materials & Methods : Using 10 adult formalin fixed cadavers, tip of mastoid process(MT) and TPs of atlas and axis were exposed bilaterally after removal of occipital and posterior neck muscles. Using standard caliper, the distances were measured from the C1 TP to the following structures : 1) exit point of VA from C1 transverse foramen, 2) branching point of muscular artery from VA, 3) entry point of VA into posterior atlanto-occipital membrane(AOM), 4) branching point of C-1 nerve. In addition, the distances were measured from the mid-portion of the posterior arch of atlas to the entry point of the VA into AOM and to the exit point of the VA from C1 transverse foramen. After removal of the ventrolateral neck muscles, neurovascular structures were exposed in the extra-jugular foraminal region. Distances were then measured from the C1 TP to the following structures : 1) just extra-jugular foraminal IJV and lower cranial nerves, 2) MT and branching point of facial nerve in parotid gland. In addition, distance between MT and branching point of facial nerve was measured. Results : The VA was located at the mean distance of 12mm(range, 10.5-14mm) from the C1 transverse foramen and entered into the AOM at the mean distance of 24mm(range, 22.8-24.4mm) from the C1 TP. The mean distance from the mid portion of the C1 posterior arch was 20.6mm(range, 19.1-22.3mm) to the entry point of the VA into AOM and 38.4mm(range, 34-42.4mm) to the exit point of the VA from C1 transverse foramen. Muscular artery branched away from the posterior aspect of the transverse portion of VA below the occipital condyle at the mean distance of 22.3mm(range, 15.3-27.5mm) from the C1 TP. The C-1 nerve was identified in all specimens and ran downward through the ventroinferior surface of the transverse segment of VA and branched at the mean distance of 20mm(range, 17.7-20.3mm) from the C1 TP. The IJV was located at the mean distance of 6.7mm(range, 1-13.4mm) ventromedially from the lateral surface of the C1 TP. The XI cranial nerve ran downward on the lateral surface of the IJV at the mean distance of 5mm(range, 3-7.5mm) from the C1 TP. Both IX and X cranial nerves were located in the soft tissue between the medial aspect of the internal carotid artery(ICA) and the medial aspect of the IJV at the mean distance of 15.3mm(range, 13-24mm) and 13.7mm(range, 11-15.4mm) from the C1 TP, respectively. The IX cranial nerve ran downward ventroinferiorly crossing the lateral aspect of the ICA. The X cranial nerve ran downward posteroinferior to the IX cranial nerve and descended posterior to the ICA. The XII cranial nerve was located between the posteroinferior aspect of the IX cranial nerve and the posterior aspect of the ICA at the mean distance of 13.3mm(range, 9-15mm) ventromedially from the C1 TP. The distance between MT and C1 TP was 17.4mm(range, 12.5-23.9mm). The VII cranial nerve branched at the mean distance of 10.2mm(range, 6.8-15.3mm) ventromedially from the MT and at the mean distance of 17.3mm(range, 13-21mm) anterosuperiorly from the C1 TP. Conclusion : This study facilitates an understanding of the microsurgical anatomy of CCJ and may help to reduce the neurovascular injury at the surgery around CCJ.

• Journal of The Korean Ophthalmological Society
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• v.59 no.11
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• pp.1024-1029
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• 2018

Purpose: We examined aqueous humor levels of 25-hydroxyvitamin D (vitamin D) in patients with age-related macular degeneration to investigate possible relationships between aqueous humor vitamin D levels and clinical manifestations. Methods: Patients > 50 years of age, 52 eyes of 34 patients with age-related macular degeneration, and 23 eyes of 17 patients treated with cataract surgery without retinal disease, were examined for aqueous humor vitamin D levels and compared. The experimental group was divided into two groups according to the median value of aqueous humor vitamin D levels. We compared the clinical manifestations of macular degeneration in both groups and identified relationships between aqueous humor vitamin D levels and clinical features. Results: Vitamin D levels in the aqueous humor were significantly lower in the experimental group than in the control group (experimental, $10.03{\pm}10.1ng/mL$ vs. control group, $40.8{\pm}16.4ng/mL$; p < 0.001). Patients with high vitamin D levels in the macular degeneration group had a higher percentage of fibrovascular pigment epithelial detachments than those in the low grade group (high grade group, 65% vs. low grade group, 27%; p = 0.003). Multiple linear regression analysis showed a significant correlation between vitamin D levels and the total number of anti-vascular endothelial growth factor intravitreal injections within 6 months (standardize coefficient, ${\beta}=-0.336$). Conclusions: Patients with wet age-related macular degeneration had significantly lower vitamin D levels in the aqueous humor compared to control group subjects of similar ages. However, in patients with macular degeneration, low vitamin D levels were associated with a greater number of intravitreal injections, while higher levels of vitamin D may lead to more advanced forms of fibrovascular retinal pigment epithelium and related low vision. These relationships were not always constant, so further studies on the relationships between local vitamin D levels and ocular disorders are needed.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.192-200
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• 2008

To evaluate the hemodynamic changes and the predictive factors of the clinical outcome in pediatric patients with moyamoya disease, we analyzed pre/post basal/acetazolamide stress brain perfusion SPECT with automated volume of interest (VOIs) method. Methods: Total fifty six (M:F = 33:24, age $6.7{\pm}3.2$ years) pediatric patients with moyamoya disease, who underwent basal/acetazolamide stress brain perfusion SPECT within 6 before and after revascularization surgery (encephalo-duro-arterio-synangiosis (EDAS) with frontal encephalo-galeo-synangiosis (EGS) and EDAS only followed on contralateral hemisphere), and followed-up more than 6 months after post-operative SPECT, were included. A mean follow-up period after post-operative SPECT was $33{\pm}21$ months. Each patient's SPECT image was spatially normalized to Korean template with the SPM2. For the regional count normalization, the count of pons was used as a reference region. The basal/acetazolamide-stressed cerebral blood flow (CBF), the cerebral vascular reserve index (CVRI), and the extent of area with significantly decreased basal/acetazolamide- stressed rCBF than age-matched normal control were evaluated on both medial frontal, frontal, parietal, occipital lobes, and whole brain in each patient's images. The post-operative clinical outcome was assigned as good, poor according to the presence of transient ischemic attacks and/or fixed neurological deficits by pediatric neurosurgeon. Results: In a paired t-test, basal/acetazolamide-stressed rCBF and the CVRI were significantly improved after revascularization (p<0.05). The significant difference in the pre-operative basal/acetazolamide-stressed rCBF and the CVRI between the hemispheres where EDAS with frontal EGS was performed and their contralateral counterparts where EDAS only was done disappeared after operation (p<0.05). In an independent student t-test, the pre-operative basal rCBF in the medial frontal gyrus, the post-operative CVRI in the frontal lobe and the parietal lobe of the hemispheres with EDAS and frontal EGS, the post-operative CVRI, and ${\Delta}CVRI$ showed a significant difference between patients with a good and poor clinical outcome (p<0.05). In a multivariate logistic regression analysis, the ${\Delta}CVRI$ and the post-operative CVRI of medial frontal gyrus on the hemispheres where EDAS with frontal EGS was performed were the significant predictive factors for the clinical outcome (p =0.002, p =0.015), Conclusion: With probabilistic map, we could objectively evaluate pre/post-operative hemodynamic changes of pediatric patients with moyamoya disease. Specifically the post-operative CVRI and the post-operative CVRI of medial frontal gyrus where EDAS with frontal EGS was done were the significant predictive factors for further clinical outcomes.