• The Journal of the Korean bone and joint tumor society
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• v.14 no.2
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• pp.95-105
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• 2008

Purpose: To identify which is the best procedure in recycling autograft according to the resection & reconstruction type and recycling methods, and so when the recycling autograft is used in limb salvage surgery. Materials and Methods: We have treated fifty-eight patients (34 male, 24 female; age range 5 to 74 years, mean age 36.5 years), who had the malignant musculoskeletal tumors, with recycling autograft (47 patients with extracoporeal irradiation, 11 patients with pasteurization) from December 1995 to February 2006. The resection and reconstruction type was 3 cases with fragmentary, 8 intercalary, 23 rAPC (recycling-Autograft-Prosthesis composite), 18 osteoarticular, 5 total joint and 1 soft tissue (achilles tendon). The result was evaluated by the radiologic union at junctional site, the functional score by musculoskeletal tumor society score and complications according to the resection & reconstruction type and recycling methods. Results: The junctional union was obtained at 15.0 months in extracoporeal irradiation and 12.6 months in pasteurization. Also the mean radiologic union was shown at 6.0 months in fragmentary, 12.8 months in intercalary, 10 months in rAPC, 23.3 months in osteoarticular and 15.6 months in total joint. The functional score was 65.5% in fragmentary, 60.8% in intercalary, 62.8% in APC (except pelvis), 66.0% in osteoarticular and 66.6% in total joint. We have experienced 1 infection, 1 prutrusio acetabuli in pasteurization (18.1%) and other 22 complications (3 deep infections, 8 nonunions, 2 fractures, 2 epiphyseal problems, 5 joint instabilities, 2 local recurrence) in extracoporeal irradiation (46.8%). Also we have experienced 3 complications (3 nonunions) in intercalary (37.5%), 9 complications (4 nonunions, 1 deep infection, 1 periprosthetic fracture, 1 epiphyseal problem, 1 local recurrence, 1 protrusio acetabuli) in rAPC (50.0%), 6 complications (2 deep infections, 2 nonunions, 1 epiphyseal problem, 1 pathologic fracture) in osteoarticular (33.3%), 5 complications (5 joint instabilities) in total joint (100%) and 1 complication(1 local recurrence) in soft tissue (100%). Conclusion: In our experience, according to the resection & reconstruction type fragmentary and intercalary may have several advantages such as good radiologic and functional result and low rate of complication. And it seems that rAPC was available in case which have no sufficient residual bone stock. Also the pasteurization may have more advantages than that of the extracorporeal irradiation.

• Journal of Chest Surgery
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• v.38 no.12 s.257
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• pp.835-843
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• 2005

Background: Cancer of the esophagus is one of the most malignant tumors with poor prognosis. The p53 gene alteration, over expression of Cyclin D1, and Ki67 index were thought to be the prognostic factors. However, their clinical significances in esophageal squamous cell carcinoma are controversial and p53 accumulation may not correlate with genetic mutation. The current study investigates their prognostic significance in squamous cell carcinoma of the esophagus. Material and Method: The Subjects studied were 124 esophageal squamous cell carcinoma patients who underwent esophagectomy. The mutation of p53, over expression of Cyclin D1, Ki67 labelling index, mitotic index were examined by using an immunohistochemical staining. We compared the results and investigated the correlation with the mutation of p53, overexpression of Cyclin D1, Ki67 labelling index, mitotic index and tumor size, and duration of survival. Result: There was no correlation between the results in immunohistochemical staining according to age, sex, tumor size, Iymph node status, and clinical stage of the disease. Mutant p53 protein was found in 69 cases (55.6$\%$). Median survival time was 21 months in cases with negative for mutant p53 protein and 22 months in positive cases. There was no significant difference in survival (p=0.46). Median survival time was 22 months in cases with negative for Cyclin D1 and 16 months in positive cases (p=0.18). Median and mean survival time was 22 months and 36 months when Ki67 labeling index was 40 or less (102 cases). Median and mean survival was 16 months and 23 months, when Ki67 labeling index was more than 40 (22 cases). There was significant difference in survival rate (p=0.011). Conciusion: Positivity of p53 and cyclin D1 was not useful in predicting the prognosis in our study. There was no significant correlation among mutant p53 protein accumulation, Cyclin D1 over expression, and Ki67 labeling index. However, in several studies, PCR single strand conformational polymorphism analysis of p53 showed a correlation to the prognosis. We thought that there was a significant discordance between p53 gene mutation and mutant p53 protein accumulation. When Ki67 labeling index was more than 40, prognosis was poorer, Ki67 seems to be a prognostic factor in our study. Therefore, we confirmed the possibility of using molecular markers as prognostic factors.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.142-150
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• 2005

Background : Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. Method : Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. Result : Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. Conclusion : The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.69-78
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• 1995

Seventy four patients with soft tissue sarcomas treated by postoperative radiotherapy in the Department of Therapeutic Radiology, Seoul National University Hospital between August 1979 and September 1990 were analyzed. The follow-up Period ranged from 3 to 145 months with a median of 51 months. Liposarcoma and malignant fibrous histiocytoma(MFH) constituted $54\%$ of the cases and the histologic grades of tumors are as follows: grade I, 23 cases; grade II, 17 cases; grade III, 24 cases: unknown grade, 10 cases. The patients were treated by marginal(17 cases), wide(55 cases) or compartmental(2 cases) excision followed by Postoperative radiotherapy. The total radiation doses were 4200-8820 cGy (median 6000 cGy), 180-200 cGy daily. 5 times per week. Of 74 Patients, 35 ultimately failed. The local control was $62.2\%$ at 5 years and cumulative risk of distant metastasis was $22,3\%$ at 5 years. The overall survival and disease free survival were $72.3\%$, and $53.3\%$ at 5 years, respectively. Survival after appearance of metastasis was $15.1\%$ at 3 years. Patients with liposarcoma experienced better local control than those with other histologic type and tumor grade and surgical resection margin significantly correlated with local recurrence, distant metastasis and overall survival on univariate analysis. In conclusion, re-excision is needed for patients with positive surgical resection margin to improve local control and further therapeutic measures using effective chemotherapy should be explored in the hope of improving overall survival.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.9
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• pp.1451-1456
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• 2004

Amino acid transporters play an important role in supplying nutrients to normal and cancer cells for cell proliferation. System L is a major transport system responsible for the $Na^+$ -independent, large neutral amino acids including several essential amino acids. L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed presumably to support their continuous growth and proliferation in malignant tumors. In the present study, we have examined the correlation between the expressions of amino acid transporter LAT1 mRNA and its subunit 4F2hc mRNA and the amount of L-leucine transport in various human cancer cell lines. Northern blot analysis have revealed that the 26 human cancer cell lines expressed LAT1 mRNA and 4F2hc mRNA. There were the differences for the levels of LAT1 and 4F2hc mRNA expressions in the 26 human cancer cell lines. The 26 human cancer cell lines transported the L-[$^{14}C$]leucine into the cells via amino acid transporter. In the 26 human cancer cell lines, a linear relationship was observed between the expression of amino acid transporter LAT1 mRNA and the amount of L-leucine transport. Little relationship was observed between the expression of 4F2hc mRNA and the amount of L-leucine transport, but the statistical significance of difference was not detected. These results indicate that the 26 human cancer cell lines express LAT1 mRNA and 4F2hc mRNA and there is the correlation between the expression of amino acid transporter LAT1 mRNA and the amount of L-leucine transport. In addition, specific inhibition of LAT1 in cancer cells will be a new rationale for anti-cancer therapy.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.201-208
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• 2007

Purpose: We investigated whether the diagnostic performance of SPECT scintimammography (SMM) can be improved by adding computer-aided diagnosis (CAD) of ultrasonography (US). Materials and methods: We reviewed breast SPECT SMM images and corresponding US images from 40 patients with breast masses (21 malignant and 19 benign tumors). The quantitative data of SPECT SMM were obtained as the uptake ratio of lesion to contralateral normal breast. The morphologic features of the breast lesions on US were extracted and quantitated using the automated CAD software program. The diagnostic performance of SPECT SMM and CAD of US alone was determined using receiver operating characteristic (ROC) curve analysis. The best discriminating parameter (D-value) combining SPECT SMM and the CAD of US was created. The sensitivity, specificity and accuracy of combined two diagnostic modalities were compared to those of a single one. Results: Both SPECT SMM and CAD of US showed a relatively good diagnostic performance (area under curve = 0.846 and 0.831, respectively). Combining the results of SPECT SMM and CAD of US resulted in improved diagnostic performance (area under curve =0.860), but there was no statistical differerence in sensitivity, specificity and accuracy between the combined method and a single modality. Conclusion: It seems that combining the results of SPECT SMM and CAD of breast US do not significantly improve the diagnostic performance for diagnosis of breast cancer, compared with that of SPECT SMM alone. However, SPECT SMM and CAD of US may complement each other in differential diagnosis of breast cancer.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.6
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• pp.444-450
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• 2008

Purpose: The aim of this study was to evaluate the usefulness of whole body positron emission tomography (PET) using $^{18}F-fluorodeoxyglucose$ ($^{18}F-FDG$) for cancer screening in asymptomatic subjects. Materials and Methods: The subjects were 1,762 men and 259 women who voluntarily underwent $^{18}F-FDG$ PET for cancer screening as a part of a routine health examination. Final diagnosis was decided by other diagnostic studies, pathological results or clinical follow-up for 1 year. Results: Of 2,021 subjects, 40 (2.0%) were finally proved to have cancer. Abnormal focal $^{18}F-FDG$ uptake suggesting malignancy was found in 102 subjects (5.0%). Among them, 21 subjects (1.0%) were proved to have cancer. Other tests in the routine health examination could not find 9 of 21 cancers (42.9%) detected by PET. The sensitivity, specificity, positive predictive value, and negative predictive value of PET for cancer screening were 52.5%, 95.9%, 20.6%, and 99.0%, respectively. Pathologies of cancers missed on PET were adenocarcinoma (n = 9; 3 colon cancers, 3 prostate cancers, 2 stomach cancers, and 1 rectal cancer), differentiated thyroid carcinoma (n = 6), bronchioalveolar cell carcinoma (n = 2), urinary bladder cancer (n = 1), and melanoma (n = 1). More than half of cancers which were not detected by PET were smaller than 1 cm in diameter. Conclusion: $^{18}F-FDG$ PET might be useful for cancer screening in asymptomatic subjects due to its high specificity and negative predictive value and playa supplementary role to the conventional health check-up, but it could not replace due to limited sensitivity for urological cancers, small-sized tumors and some hypometaboic cancers.

• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.1
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• pp.35-42
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• 2018

Purpose Standardized uptake value(SUV) has been widely used as a quantitative metric of uptake in PET/CT for diagnosis of malignant tumors and evaluation of tumor therapy response. However, the SUV depends on various factor including PET/CT scanner specifications and reconstruction parameter. The purpose of this study is to validate a EQ PET to evaluate SUV across different PET/CT systems. Materials and Methods First, NEMA IEC body phantom data were used to calculate the EQ filter for OSEM3D with PSF and TOF reconstruction from three different PET/CT systems in order to obtain EARL compliant recovery coefficients of each spheres. The Biograph true point 40 PET/CT images were reconstructed with a OSEM3D+PSF reconstruction, images of the Biograph mCT 40 and Biograph mCT 64 PET/CT scanners were reconstructed with a OSEM3D+PSF, OSEM3D+TOF, OSEM3D+PSF+TOF. Post reconstructions, the proprietary EQ filter was applied to the reconstruction data. Recovery coefficient can be estimated by ratio of measured to true activity concentration for spheres of different volume and coefficient variability(CV) value of RC for each sphere was compared. For clinical study, we compared SUVmax applying different reconstruction algorithms in FDG PET images of 61 patients with lung cancer using Biograph mCT 40 PET/CT scanner. Results For the phantom studied, the mean values of CV for OSEM3D, OSEM3D+PSF, OSEM3D+TOF and OSEM3D+PSF+TOF reconstructions were 0.05, 0.04, 0.04 and 0.03 respectively for RC. Application of the proprietary EQ filter, the mean values of CV for OSEM3D, OSEM3D+PSF, OSEM3D+TOF and OSEM3D+PSF+TOF reconstructions were 0.04, 0.03, 0.03 and 0.02 respectively for RC. Clinical study, there were no statistical significance of the difference applying EQ PET on SUVmax of 61 patients FDG PET image. (p=1.000) Conclusion This study indicates that CV values of RC in phantom were decreased after applying EQ PET for different PET/CT system and The EQ PET reduced reconstruction dependent variation in SUVs for 61 lung cancer patients, Therefore, EQ PET will be expected to provide accurate quantification when the patient is scanned on different PET/CT system.

• The Journal of the Korean bone and joint tumor society
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• v.1 no.1
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• pp.38-44
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• 1995

Metastatic bone tumor is the most common bone tumor and 32.5% of all primary malignant tumors are eventually metastasize to bone. Metastatic bone tumor has been more frequently encountered disease in the orthopedic fields due to the greater longevity of life of the patients with primary visceral cancers by major advances in early detection, diagnosis, and surgical/radiotherapeutic/chemotherapeutic treatment of primary and metastatic lesions. Therefore, the epidemiologic data about the incidences and the patterns of bone metastasis is important. We reviewed 417 patients who were diagnosed and treated for metastatic bone tumor at Kosin University Medical Center from 1985 to 1993 to analyse the primary lesion, age and sex distributions, location of bone metastasis, patterns of metastasis according to the primary. The results were as follows : 1. The common origin of bone metastasis were lung(29.5%), stomach(15.3%), breast(11.3%), unknown(7.7%), cervix(5.3%), liver(4.8%) in order of frequency. 2. There were 251 men and 166 women and their mean age was 54.8 years and the peak age incidence was in 6th decades. Most cases(85.3%) were occured beyond 5th decades. 3. The preferred sites of metastatic deposits were spine(64.0%), pelvis(40.5%), rib(38.8%), femur(36.7%), skull(21.1%), humerus(13.9%), scapula(13.0%) in order of frequency. In the spine, thoracic(42.1%), lumbar(39.1%), cervical(13.2%), sacral(5.6%) vertebrae were involved in order of frequency. 4. Multiple bone metastases were more common(73.1%) than single metastasis(26.9%). 5. In the lung cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, pelvis, femur. 6. In the stomach cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, femur, pelvis. 7. In the breast cancer, the peak age incidence was 5th decades, and the preferred sites of bone metastasis were spine, rib, pelvis. 8. In the bone metastasis with unknown primary site, the peak age incidence was 7th decades, the preferred sites of bone metastasis were spine, femur, pelvis, and the common histologic types were adenocarcinoma and squamous cell carcinoma.