Oral squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its high metastasis and recurrent rates and poor prognosis. Taxol is an anticancer agent which is microbial products extracted from jew tree. It combines with the tubulin and induces apoptosis by inhibiting mitosis of cell with microtubule stabilization. Recently, it was reported to be effective in various solid tumors, but only very slight effect has been seen in oral squamous cell carcinomas due to its cell-specific potencies. Cyclosporin A is used as immune suppressant and is being applied in anticancer therapy as its mechanism of induction of change of apoptotic process in various cells have been known. In this study, oral squamous cell carcinoma HN22 cell line was used for in vitro experiment and as for the experimental group taxol and cyclosporin A were applied alone and to observe the synergistic effect of apoptosis, Taxol and cyclosporin A were coadministered with different concentration of taxol for comparison. The results were obtained as follow: 1. There was no difference in Bcl-2, Bax, caspase 3, 8, 9 mRNA expression when cyclosprin A or taxol was applied alone to HN 22 cell line. 2. Caspase 3, 9 mRNA expression was prominently increased when cyclosprin A and taxol were applied together to cancer cell. 3. No significant difference was observed when cyclosporin A and taxol($1{\mu}g/ml$ and $3{\mu}g/ml$) were applied together to cancer cell line. 4. No significant difference was seen in Bcl-2, Bax, and caspase 8 mRNA expression in all the groups of in vitro experiments. 5. When cyclosporin A was applied alone in vivo study on the nude mice, histopathologi cal findings was similar to those of the control group. Oral squamous cell carcinoma induced by inoculation of HN 22 cell line was not reduced after treatment of cyclosporin A. 6. When taxol was applied alone, the islands of squamous cell carcinoma still remained, which meant insignificant healing effect. There was a lesser volume increase compared with the cyclosporin A alone. 7. When taxol and cyclosporin A were applied together, the connective tissue and calcification were seen in the histopathologic findings. Oral squamous cell carcinoma was decreased and cancer cell was disappeared. In observing the tumor mass change with time, there was a gradual decreased size and healing features. As the results of the in vitro experiment, it could conclud that only when the two agents are applied together, mitochondria-mediated apoptosis occurred by considerable increase of caspase 3, 9 mRNA expression, irrespectable of the concentration of taxol. In vivo experiment, there was a discrete synergistic effect when the two agents were applied together. But single use of cyclosporin A was not effective in this study. Based on the results of this experiment, if further clinical studies are done, taxol and cyclosporin A could be effectively used in treatment of oral squamous cell carcinomas.
The objectives of this study was to explore the growth pattern of the oral squamous cell carcinoma when overexpressed COX was inhibited, explore the pathway that COX inhibitors suppressed the proliferation of cancer cells, and then hereafter investigate the potential of COX as chemopreventive target for oral squamous cell carcinoma. For confirming the COX-dependent effect and mechanisms on growth of the oral cancer cells, we treated the nonselective NSAID, Mefenamic acid and COX-2 selective inhibitor, Celecoxib in HN4 cell line. And then the cell line was evaluated with MTT assay and growth curve, the production of PGE2, total RNA extraction and RT-PCR analysis, and TEM The results were obtained as follows: 1. After administration of medication, in the result of MTT assay, Celecoxib inoculated group inhibit the cell growth rather than Mefenamic acid inoculated group. 2. The growth curve of cell line showed as time passes by there was a dramatic cell growth in the control group, and gradual growth inhibition was found in medication inoculated group and, in Celecoxib inoculated group there was more inhibition of cell growth. 3. After the administration of medication, Celecoxib tend to inhibit the synthesis of PGE2 more than Mefenamic acid. Mefenamic acid inhibit the synthesis of PGE2 more as the concentration gets high, but Celecoxib inhibited the synthesis of PGE2 even in low concentration. 4. After the administration of medication, the revelation of COX mRNA in cell line, there was a 50% decrease in COX-1, 60% decrease in COX-2 as in $50{\mu}M$ Mefenamic acid, and in Celecoxib $50{\mu}M$ there was not much difference in COX-1 and 90% decrease in COX-2 was found. 5. HN4 cell line showed broken nucleus and tangled cytoskeleton bundles in cytoplasm which meant apoptotic features after the treatment of Celecoxib in TEM view. Depending on the above results, we estimate that the inhibition of the expression of COX-2 cause the growth suppression of the oral squamous cell carcinoma, and it get achieved through pathway of reduced PGE2 production and increased apoptosis. In addition to, because COX-2 selective inhibitor specifically act to COX-2, it is considered that COX-2 selective inhibitor has the adequate potential as chemopreventive agent for oral squamous cell carcinoma.
Purpose : This study was designed to evaluate the clinical aspect of cysts which arised in the oral and maxillofacial region. Patients and Methods : We reviewed clinical record, radiograph, histopathologic and operative report of 155 patients who had been diagnosed as cysts and treated at the department of oral and maxillofacial surgery in Chonnam National University Hospital from January 2003 to December 2008. Gender, age, classifiaction, anatomic distribution, clinical sign and symptoms, treatment, complications and recurrence rate were studied. Results : 1. Among 155 patients, the male patients(64.5%) were more than the female(35.5%). 2. The average age ofthe patients was 37.2 years(ranging from 5 to 79 years). 3. In pathologic classification, radicular cyst and dentigerous cyst were most common cysts, irrespective of 73 cases(48.3%) and 35 cases(23.2%). 4. The frequently involved cystic regions were followed as mandibular molars(38.1%), and maxillary incisors(30.2%). 5. The frequent sequence of clinical symptoms was edema(29.9%), no symptom(18.9%), tenderness(13.9%), pain(11.5%) and abscess(9.4%). 6. The most prevalent treatment was the combination operation, such as cyst enucleation with extraction or endodontic treatment of the causative tooth(76.8%) 7. Among 155 cases, 2 cases that were treated using enucleation method were recurred(1.3%).
The purpose of this study was to investigate the factors affecting the postsurgical mandibular stability for both one- and two jaw surgery. 18 for one-jaw surgerys and 24 for two-jaw surgerys among skeletal class III malocclusion patients who experienced orthodontic treatment and orthognathic surgery at Pusan National University Hospital were selected. Lateral cephalograms taken at the first visit, after presurgical orthodontic treatment, immediately after surgery and follow-up over 6 months, were traced. Based ANOVA, multiple linear regression analysis was completed for one-jaw surgery with postsurgical stability as the criterion and the magnitude of mandibular setback, the change of mandibular incisor height during surgery, the changes of mandibular plane angle and mandibular incisor angle during presurgical orthodontic treatment as affecting factors. Same analysis was completed for two-jaw surgery with postsurgical stability as the criterion and the magnitude of mandibular setback as affecting factor. The results were as follows : 1. In the one-jaw surgery cases, the magnitude of mandibular setback, the change of mandibular incisor height during surgery, the changes of mandibular plane angle and mandibular incisor angle during presurgical orthodontic treatment explained the variability in postsurgical stability with a significant $R^2$ value of 0.84. 2. In the two-jaw surgery cases, the magnitude of mandibular setback explained the variability in postsurgical stability with a significant $R^2$ value of 0,28.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.28
no.5
/
pp.372-382
/
2002
As the most of dentofacial deformity patients indicated to orthognathic surgery have strong desire for esthetic improvement as well as functional improvement, ideal esthetic evaluation should be made at surgical prediction. Lateral cephalographs has been commonly used for surgical prediction, however, remarkable discrepancy between esthetic viewpoint by simple looking and analysis on lateral cephalographs often found on evaluation of sagittal position of the upper and lower jaws especially in cases of mandibular prognathism of Koreans. In these cases, we have been employed Esthetic NaP(ENaP)-line for corrective evaluation and ideal surgical prediction on lateral cephalographs, but the efficacy of ENaP-line has not been evaluated. This is a study on efficacy of ENaP-line for orthognathic surgery of Korean mandibular prognathism. 170 Korean patients who had been diagnosed as mandibular prognathism and planned for orthognathic surgery at Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University during last 10 years are studied. The obtained results are as followings; among 170 patients of mandibular prognathism, 132 patients(77.6%) had not discrepancy in evaluation of sagittal position of the maxilla between cephalometric and esthetic evaluation(they are classified as Group I), however, 38 patients(22.4%) had definite discrepancy(they are classified as Group II). ENaP-line was employed in all cephalometric analysis of Group II. The proportions of male and female were similar in both Groups. Sixteen vertical reference lines perpendicular to 16 horizontal reference lines were obtained as followings; Each of the representative degree of ${\angle}SN/AFH$, ${\angle}SN/CFH$ and ${\angle}AFH/CFH$ obtained at Group I was applied to SN plane, AFH plane and CFH plane of Group II each other, and so 16 horizontal reference lines could be obtained individually according to each of the applied degree to each plane. And then their reliability to coincide with ENaP-line of Group II was evaluated. A vertical reference line perpendicular to a horizontal line made by application of the representative degree of ${\angle}$AFH/CFH in Group I to AFH line in Group II had the most highest coincidence with ENaP-line of Group II, however, its agreement was 42% in male and 47% in female. From this results, the rest of them should be determined their corrective jaw position definitely depend on
Kim, Sang-Woo;Hwang, Kyung-Gyun;Lim, Byung-Sup;Park, Chang-Joo;Chung, Il-Hyuk;Paik, Seung-Sam;Shim, Kwang-Sup
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.32
no.4
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pp.360-373
/
2006
The purpose of this research was to investigate whether pulsed electromagnetic field (PEMF) stimulation applied to the rabbit cranial defects grafted with ${\beta}$-tricalcium phosphate (${\beta}$-TCP) could affect the new bone formation. With 16 New Zealand white rabbits under the same condition, bilateral calvarial bone defects were formed around the sagittal suture line. The defect on the left side was grafted with ${\beta}$-TCP, while on the right side was grafted by harvested autogenous bone. PEMF was applied to 8 rabbits for 8 hours per day. The bony specimen were divided into 3 groups, the group 1 was autogenous bone grafted specimen, the group 2 was ${\beta}$-TCP grafted with PEMF, and the group 3 was ${\beta}$-TCP grafted without PEMF. We investigated the bone regeneration & growth factor expression at 2, 4, 6, and 8 weeks. As a result, BMP 2 was expressed in the group 1 from 2 weeks, the group 2 from 4 weeks, and the group 3 from 6 weeks. BMP 4 was expressed in the group 1 from 2 weeks, in the group 2 and the group 3 from 4 weeks. 4. There was no significant difference in expression pattern of BMP 7, PDGF, VEGF, and TGF-${\beta}$1 during grafted bone regeneration in group 1, 2, and 3. According to our results, PEMF stimulation could be effective on the new bome formation in animal study, and have a feasibility of clinical use.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.32
no.4
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pp.295-307
/
2006
Styela clava, called non-native tunicate or sea squirt, is habitat which include bays and harbors in Korea and several sites in the sea faced world. We fabricate cellulose membrane nerve conduit (CMNC) from this native sea squirt skin, and evaluate the capacity of promoting peripheral nerve regeneration in the rat sciatic nerve defect model. After processing the pure cellulose membrane from the sea squirt skin as we already published before, CMNC was designed as a non-tubular sheet with 14 mm length and 4 mm width. Total eleven male Spraque-Dawley rats (12 weeks, weighing 250 to 300g) were divided into sham group (n=2), silicone tube grafted control group (n=3) and experimental group (n=6). Each CMNC grafted nerve was evaluated after 4, 8 and 12 weeks in the experimental group, and after 12 weeks, sciatic function was evaluated with sciatic function index (SFI) and gait analysis, and histomorphology of nerve conduit and the innervated tissues of sciatic nerve were all examined using image analyzer and electromicroscopic methods in the all groups. The regenerated axon and nerve sheath were found only in the inner surface of the CMNC after 4 weeks and became more thicker after 8 and 12 weeks. In the TEM study, CMNC grafted group showed more abundant organized myelinated nerve fibers with thickened extracellular matrix than silicone conduit grafted group after 12 weeks. The sciatic function index (SFI) and ankle stance angle (ASA) in the functional evaluation were $-47.2{\pm}3.9$, $35.5^{\circ}{\pm}4.9^{\circ}$ in CMNC grafted group (n=2) and $-80.4{\pm}7.4$, $29.2^{\circ}{\pm}5.3^{\circ}$ in silicone conduit grafted group (n=3), respectively. And the myelinated axon was 41.59% in CMNC group and 9.51% in silicone conduit group to the sham group. The development of a bioactive CMNC to replace autogenous nerve grafts offers a potential and available approach to improved peripheral nerve regeneration. As we already published before, small peptide fragment derived from the basement membrane matrix proteins of squirt skin, which is a kind of anchoring protein composed of glycocalyx, induced the effective axonal regeneration with rapid growth of Schwann cells beneath the inner surface of CMNC. So the possibilities of clinical application as a peripheral nerve regeneration will be able to be suggested.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.32
no.4
/
pp.317-326
/
2006
Purpose : The aim of this study was to evaluate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) injected on the rate of new-bone formation for distraction osteogenesis on dogs. Materials & Methods : Twelve adult dogs were randomly selected into two groups of six dogs on each. Unilateral osteotomies were performed on the body of the mandible and an intraoral distractor was mounted to the mandible on dogs. One group was treated with injection of rhBMP-7 and the other group served as the control. RhBMP-7 was administered on the day of surgery by single injection into the medullary bone at the osteotomy gap. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. The animals were then sacrificed at 2, 4, and 8 weeks after completion of the distraction. Two dogs in each group, totaling four dogs, were killed at 2 weeks, 4 weeks, and 8 weeks after completion of distraction, respectively. The lengthened mandibles were harvested and processed for radiographic and histological examinations. In addition, immunohistochemical examination using osteocalcin expression was studied. Results : Radiographs showed accelerated regenerate ossification with maturation of new bone in the rhBMP-7 group comparing with the control group at the 4 weeks of the consolidation. There was no significant difference in the radiographic findings at the 2 weeks and 8 weeks of the consolidation period. Histological findings demonstrated increased bone healing pattern in the rhBMP-7-treated group during all observation period. The expression of osteocalcin immunoreactivity was hardly detected in the normal mandible of dog, but the expression was detected in all experimental rhBMP-7 treated specimens. There were also significant increasing in number of positive immunostaining cells and staining intensity of osteocalcin expression in the rhBMP-7 treated group compared with those of the control group on 2-weeks and 4-weeks. There was a significant decreasing in staining intenstiy of all both two groups on 8 weeks of consolidation period, but significant differences of immunostaining was not seen in two groups. Conclusions : A single injection of rhBMP-7 at the time of osteotomy may stimulate the rate of regenerate ossification and increase callus maturation during distraction osteogenesis. In addition, it may shorten the distraction osteogenesis procedure and decrease the prevalence of complications associated with mandibular distraction osteogenesis.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.31
no.6
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pp.461-467
/
2005
Background. 5-(and-6)-carboxy-2',7'-dichlorofluorescein diacetate, succinimidyl ester mixed (CFSE) is the fluorescent labelling agent of living cells and used to trace the cells in vivo after transplatnation of various cells. The CFSE labelled cells can maintain fluorescence for up to 7 days after labelling. The MC3T3-E1 cell line (MC3T3) has been used for many studies about osteoblast, which is well known as a mouse preosteoblast. So the CFSE would be used to trace the transplanted MC3T3. However there are few reports about CFSE labelling of MC3T3. This study is aimed to know about adequate concenturation and incubation time of CFSE to MC3T3. Materials and methods. The MC3T3 was incubated in a humidified atmosphere of 95% air with 5% $CO_2$ at $37^{\circ}C$ using ${\alpha}$-minimal essential medium (${alpha}$-MEM) containing10% FBS and gentamycin. Ten mM CFSE solution in dimethylsulphoxide (DMSO: 1%) was diluted with phosphate buffered saline (PBS) and final concentration of culture medium was, respectively, 5, 10, 15, 20, 25 and 30 ${{\mu}M$. Then the MC3T3 was incubated with CFSE in a humidified atmosphere of 95% air with 5% $CO_2$ at $37^{\circ}C$ for 5, 10, 15, 20, 25, 30, 35, 40 and 45 minutes in each concentration. The fluorescence of CFSE labelled cells was analysed with a inverted fluorescence microscope. The duration of cell labelling was also studied. Trypan blue dye exclusion test was done for cell viability. Results. For concentration between 5 and 10 ${\mu}M$, CFSE did not significantly label the MC3T3 in vitro. The destruction of MC3T3 was observed at the concentration of 20 ${\mu}M$. In the concentration of 15 ${\mu}M$, the best labelling was obtained at an incubation period between 15 and 30 minutes. The MC3T3 labelled with an incubation period of 15 minutes at 15 ${\mu}M$ was still fluorescent 7 days after CFSE labelling. The mean cell viability was 95.93%. Conclusion. These results suggests an incubation period of 15 minutes at 15 ${\mu}M$ of CFSE provides best labelling of MC3T3 in vitro.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.29
no.1
/
pp.26-34
/
2003
Intraoral Vertical Ramus Osteotomy,along with Sagittal Split Ramus Osteotomy,is an popular surgical technique performed on mandibular prognathism. However Intraoral Vertical Ramus Osteotomy has been suspected for an initial mobilization at the healing phase of segment because it does not employ the rigid fixation between segments. To execute a study on the healing phase of segment after Intraoral Vertical Ramus Osteotomy on the horizontal plane, 102 patients (204 parts) who were diagnosed mandibular prognathism and took Intraoral Vertical Ramus Osteotomy at the Yonsei University dental hospital were observed during the period of before operation, immediately postoperation, 1 month, 3 months, 6 months, and 12 months. The change in the width of segment and horizontal angle of proximal segment and condylar head on the Submentovertex Cephalogram taken from those patients represented following results. 1. The width of proximal and distal segment decreased with the lapse of time. It decreased into 84.5% between immediate postoperative and 6M and even continued to decrease till 12M. 2. The horizontal angle of the proximal segment did medial rotation according as the lapse of time and rigorously continued till 3M. The rotation angle of condylar head indicated its tendency of recurrence to the original position but the entire recurrence was not allowed. The bigger an initial angle was, the higher was the tendency of recurrence after the operation while the rotation angle remained still bigger. 3. After grouping into group 1, group 2,and group 3 based on the extent of the variation of rotation angle of condylar head at immediate postoperative, the variation of rotation angle was measures in each group. The result presented that the initial rotation angle of condylar head had correlation with that of proximal segment but had no relation with the extent of setback of the mandible. However a quantitative analysis alone is not a sufficient method for analyzing the healing phase of segment on the horizontal plane.Therefore a multilateral analysis using 3 dimensional data such as CT is recommendable for the future study.
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