• Radiation Oncology Journal
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• v.16 no.3
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• pp.225-231
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• 1998

Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.15 no.1
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• pp.63-79
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• 1993

To repair bony defects with tansplanted bone in the body, fresh autogenous bone is undoubtly, the most effective bone graft for clinical applications. But the demineralized bone has the matrix-induced bone formation which was suggested by Urist in 1965. Many authors assisted that demineralized bone powder induces phenotypic conversion of mesenchymal cells into osteoblasts, with high-density bone formation. The process of inducing differentiated cells becomes osteogenic properties. The purpose of this study was to evaluate the osteoinductive capacity of allogenic freeze-dried demineralized bone block (FDD, $7{\times}7mm$) and to compare FDD with the same sue of deep-frozen allogenic bone(DF), fresh autogenous bone (A) after implantation. The histological and ultrastructural features of tissue responses were examined after 1, 2, 4, 6, 8 weeks implantation of each experimental groups in the operative site of the New Zealand white rabbits. The results were as follows : 1. Inflammatory cell infiltration generally has appeared at 1 week, but reduced at 4 weeks in each group, but most severe in DF group. 2. Osteoblastic activity has increased for 4 weeks, but decreased at 6 weeks in each group and there was no significant difference among experimental groups. 3. New bone formation has begun at 1week, least activations in A groups, and showed the revesal line of bone formation among each group at 6 to 8 weeks. 4. Bone resorption has appeared at 1 week, but disappeared at 4 weeks in both A and DF groups, but more severe in DF than A groups. 5. In ultrastructural changs, the DF group have showed the most remarkable osteoclastic activities among experimental groups. 6. Osteoid or tangled collagen fibrils near the implanted sites were replaced by more mature, lamellated bony trabeculae during bone remodeling. There was little difference among each experimental groups. 7. During the convertion osteoblasts to osteocytes which embedded within the bone matrix, there was organ-less-poor cytoplasm, increased nuclear chromatin, abundant rough endothelial reticulum (RER) in each groups. From the above the findings, the DF group shored more bone resorption and foreign body reaction than FDD and A groups, and FDD group showed more new bone formation or osteoblastic activity than DF and A groups in early stage. There was no significant difference of cellular activities among the FDD DF, and A groups according to the time.

• Journal of Periodontal and Implant Science
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• v.29 no.3
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• pp.469-484
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• 1999

The purpose of this study was to evaluate new bone formation following guided bone regeneration by resorbable and nonresorbable membrane. Six adult mongrel dogs were used. The first, second, third, fourth premolars in the mandible of each dog were extracted. Two months after tooth extraction, a buccal dehiscence defect was surgically created on each edentulous area. The experimental sites were divided into three groups according to the treatment modalities ; Group I-a: surgical treatment only ; Group I -b: allogenic decalcified freezed dried bone grafting ; Group II-a : e- PTFE membrane placement only ; Group II-b : allogenic decalcified freezed dried bone grafting and e-PTFE membrane placement ; Group III-a : Vicryl(R) mesh placement only ; Group III-b : allogenic decalcified freezed dried bone grafting and Vicryl(R) mesh placement . The animals were sacrificed at 8 weeks after operation and the specimens were prepared for histologic and histometric examination. The results were as follows : Clinically, all defect sites were healed without exposure of barrier membrane after the eight weeks. In Group I-a, dense connective tissues were impinged in the bony defect area. Well vascularized and fibrous bone marrow indicated that bone formation was still taking place was found. In Group I-b, in areas closer to the periphery, lamellation of the newly formed bone would found. In Group II-a, beneath the e-PTFE membrane a dense layer of connective tissue covering the most external portions of the regenerated tissue was seen. The new bone surfaces were lined with osteoid and osteoblast. In Group II-b, a dense layer of connective tissue covering the most external portions of the regenerated tissue was observed beneath the e-PTFE membrane. A notable amount of alveolar ridge regeneration was seen with new rigdes with well-contoured form. In Group III-a, the new bone surface were lined with osteoid and osteoblast, indicating active bone formation. A clear demarcation could not be noted between the host bone and new bone. In Group III-b, a notable amount of alveolar ridge regeneration was seen with new ridges assuming wellcontoured form. In areas closer to the periphery, lamellation of the newly formed bone would found. As histometric examination, the amount of bone formation was gained from $12.8mm^2$ to $26.3mm^2$. It was significantly greater in group II-b and group III-b compared to other groups(p<0.05) . These results suggest that Vicryl(R) mesh after DFDB grafting used in guided bone regeneration could create and sustain sufficient space for new bone formation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.353-359
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• 2010

Introduction: This study examined the effect of cyclosporine A (CsA) on the allogenic cranial bone graft in the mice. Materials and Methods: Twenty eight 12-week-old male ICR mice weighing 40 g were used. The experimental group was injected subcutaneously with CsA (10 mg/kg/day) diluted in Caster oil for 7 days prior to the graft until sacrifice. The control group was injected with the same solution without CsA. Two full-thickness bone defects with a diameter of 3 mm were made with a trephine bur in the parietal bone lateral to the sagittal suture. A calvarial defect of a mouse was grafted with allogenic calvarial bone disc from another mouse. The experimental and control groups were injected with CsA and the solution without CsA in the same manner before surgery, respectively. The mice were sacrificed at 1 week, 2 weeks and 4 weeks after the bone graft, respectively. Results: In the experimental group, fibrous connective tissues and small amounts of inflammatory cells were observed. At 2 weeks after the allograft in the experimental group, new bone formation in fibrous collagenous tissue and around the allogenic bone was noted. At 4 weeks after the allograft, new bone formation was active along and at the periphery of the mature allogenic bone. The proliferation of blood vessels increased in bone marrow. In the control group, fibrous tissues and inflammatory cells were observed around the allogenic bone and existing bone at 1 week. At 2 weeks after the allograft, the proliferation of blood vessels accompanied by inflammatory cells were scattered in the fibrous connective tissues. New bone formation around the allogenic and existing bone could be observed. At 4 weeks after the allograft, inflammatory cells were severely infiltrated around the allogenic bone. Osteoclasts were scattered along the allogenic bone and induced bone resorption. Conclusion: These results suggest that the daily administration of CsA (10 mg/kg/day) induces efficient immunosuppression without serious complications, and this protocol might be useful for the experimental model of allogenic bone grafts.

• Archives of Plastic Surgery
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• v.37 no.5
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• pp.555-560
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• 2010

Purpose: Facial allotransplantation (FA) could provide an excellent alternative to current treatments for facial disfigurement. However, despite being technically feasible, there continues to be various ethical and psychosocial issues associated with the risks and benefits of performing FA. The purpose of this study is to investigate risk acceptance and expectations in FA. Methods: In a quantitative assessment of risk versus benefit with respect to FA, from 2004 to 2008, Barker et al. developed and published a questionnaire-based instrument (Louisville Instrument for Transplantation [LIFT]), which contained 237 standardized questions. In the current study, the authors assessed risk versus benefits and expectations of FA using a Korean version of the LIFT. Respondents in three study groups (lay public, n=140; medical students, n=120; doctors, n=34) were questioned about risk acceptance as related to immunosuppression and tissue rejection, and expectations as related to quality of life improvement, and functional and aesthetic outcomes. A summary of the data has been provided and statistical analyses were performed. Results: Among the three study groups, results indicated that doctors accept the least amount of risk for a facial allotransplant, followed by medical students, and finally lay public. There was a significant statistical difference in three of the four questions regarding risk acceptance between the groups (p < 0.05). In general, lay public exhibited higher expectations for facial allotransplantation than the other groups. Additionally, there was a significant statistical difference in the importance of aesthetic outcome between the groups (p < 0.05). Conclusion: The authors' data indicate the three populations have vastly different levels of risk acceptance and expectations with regard to FA. Therefore, it is very important that surgeons establish clear, open, and thorough communication with patients in their consultations regarding FA. This is particularly important with respect to whether or not a patient's level of risk acceptance and expectations are progmatic.

• Archives of Plastic Surgery
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• v.37 no.5
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• pp.509-518
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• 2010

Purpose: Major drawbacks of conventional bone marrow stromal cells (BSCs) transplantation method are mainly caused by direct transplanted cell to host cell interactions. We hypothesized that separation of the transplanted cells by a microporous membrane might inhibit most of the potential adverse effects and induce superior effect. The purpose of the study is to determine the optimal condition of the microporous membrane. Methods: First, BSCs were placed in polyethylene terephthalate (PET) transwell inserts with 3, 8, or $12{\mu}m$ pore size, and cultured in 24 well culture plates. After 5 days, bottoms of the plates were observed for presence of attached BSCs in monolayer and cell numbers were evaluated. Second, BSCs were placed PET, polycarbonate (PCT), and mixed cellulose esters (MCE) transwell inserts with 3 and $8{\mu}m$ pore size, and cultured in 24 well culture plates. After 3 days, the supernatants of the media left in culture plate were analyzed for collagen, vascular endothelial growth factor (VEGF), platelet derived growth factor BB (PDGF-BB), and basic fibroblast growth factor (bFGF). Third, BSCs were placed in 15% and 70% of the PET membrane with $3{\mu}m$ pore size. All the experimental conditions and methods were same as the second study. Results: The optimal pore sizes to prevent BSC leakage were $3{\mu}m$ and $8{\mu}m$. The amounts of type I collagen and three growth factors tested did not show significant differences among PET, PCT, and MCE groups. However, the collagen, VEGF, and bFGF levels were much higher in the high (70%) density group than in the low (15%) density group. Conclusion: This study revealed that the optimal pore size of membrane to prevent direct BSC to recipient cell contact is in between $3{\mu}m$ and $8{\mu}m$. Membrane materials and pore sizes do not influence the collagen and growth factor passage through the membrane. The most striking factor for collagen and growth factor transport is pore density of the membrane.

• Journal of Chest Surgery
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• v.31 no.6
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• pp.586-590
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• 1998

Background: The regression of the left ventricular hypertrophy after prosthetic valve replacement in patients with aortic valvular stenosis is an important factor to determine the appropriateness of the replaced prosthetic valvular size. Methods: To assess the regression of myocardial hypertrophy, a retrospective analysis of Doppler echocardiographic and electrocardiographic data was undertaken before, soon after(7.5$\pm$2.1 day), and late after(10.7$\pm$1.8 months) surgery in 36 patients(22 males, 14 female, mean age 54$\pm$12.1 years, mean BSA 1.61$\pm$0.15m2) with predominant aortic valvular stenosis. The patients underwent St. Jude Medical aortic valve replacement. By the size of the valves used, the patients were divided into three groups(19, 21 and 23+). Results: The mean body surface area(1.48$\pm$0.13) in the patients with the 19 mm valve was smaller than that in the other groups(1.63$\pm$0.12)(p<0.05). No significant changes of ejection fraction were detected in all groups over time. Left ventricular muscle mass index(gm/m2) was reduced significantly in the 21 and 23+ groups over time(p<0.05), but there were no significant changes in the 19 mm valve group. The electric voltage height on EKG at the period of late after surgery was reduced significantly in all groups(p<0.05). Conclusion: Despite clinical improvement, the LVH was not reduced significantly in 19 mm valve group. Thus we suggest that more attention and additional procedures such as annular enlargement should be taken in patients who will undergo the replacement of 19 mm prosthetic valve.

• The Journal of the Korean bone and joint tumor society
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• v.14 no.2
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• pp.157-162
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• 2008

Nowadays, most of the malignant bone tumor patient underwent limb salvage operation, however, reconstructive options for skeletally immature group are still controversial. There are three necessary conditions of most ideal reconstructive method in treating the skeletally immature children. As the epiphyseal plate sacrification is usually inevitable in malignant bone tumor around knee joint, ideal reconstructive technique would be as follows; 1)minimal or no damage to theadjacent epiphyseal plate, 2) maintaining mobile joint, 3) index procedure does not disturb subsequent operation such as lengthening. Segmental resection and reconstruction using autogenous pasteurized graft was done for 4 years old meta-diaphyseal osteosarcoma of femur. At 6 months from index operation, plain radiograph showed pasteurized bone resorption and loosening of fixation devise. To overcome the complication, we used allograft reconstruction by impacting the proximal host bone to the fluted portion of allobone. Three months later, proximal bone union was observed and patient showed good functional outcome.

• The Journal of the Korean bone and joint tumor society
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• v.1 no.2
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• pp.133-144
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• 1995

After resection of intraarticular, periacetabulum(P2) and pubic rami(P23) and extraarticular, proximal femur(P2-H12) by Enneking classification, reconstruction is very difficult. We experienced three cases of saddle prostheses for reconstruction after P2, P23, and P2-H12 resection in pelvic malignancies. Case 1 was a high grade chondrosarcoma in 36 year-old-man and P2 resection was done. But he died of disease 19 months after operation. Case 2 was a malignant giant cell tumor in 32 year-old-woman. P23 resection was given and she is disease-free 32 months after operation. Case 3 was an osteosarcoma of 27-year-old-man and P2-H12 resection was performed and he is disease-free postoperative 12 months now. According to MSTS functional evaluatin system, all three patients showed no pain(5), intermediate function(2), emotinally satisfied(3), one cane or crutch supported(1), limited walking(3), and minor cosmetic gait(3). There was no significant complication and no dislocation except intermittent inguinal hernia in case 2. All patients started crutch walking 3 weeks after operation. Around 6 months postoperatively, the preserved iliac wing(P1 component) was hypertrophied enough to endure the full weight bearing. All could have squating and kneeling positions. In conclusion, saddle prosthesis would be a very useful method of reconstruction after P2, P23, and/or H1-2 resection to shorten the operation time and to reduce the infection rate without significant loss of function.